Identification
- Summary
Amitriptyline is a tricyclic antidepressant indicated in the treatment of depressive illness, either endogenous or psychotic, and to relieve depression associated anxiety.
- Brand Names
- Elavil
- Generic Name
- Amitriptyline
- DrugBank Accession Number
- DB00321
- Background
Amitriptyline is a tricyclic antidepressant that has been used to treat depression for decades. ELAVIL, a previously approved branded product of amitriptyline, was first approved by the FDA in 1961.11 Amitriptyline has been investigated in the treatment of pain-related conditions, attributed to its analgesic properties.6
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Amitriptyline (DB00321)
- Weight
- Average: 277.4033
Monoisotopic: 277.183049741 - Chemical Formula
- C20H23N
- Synonyms
- 10,11-dihydro-5-(γ-dimethylaminopropylidene)-5H-dibenzo(a,d)cycloheptene
- 10,11-dihydro-N,N-dimethyl-5H-dibenzo(a,d)heptalene-Δ5,γ-propylamine
- 3-(10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine
- 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethylpropan-1-amine
- 5-(3-dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptatriene
- 5-(3-dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptene
- 5-(γ-dimethylaminopropylidene)-5H-dibenzo[a,d][1,4]cycloheptadiene
- Amitriptilina
- Amitriptylin
- Amitriptyline
- Amitriptylinum
- External IDs
- MK 230
- N 750
- Ro 4-1575
Pharmacology
- Indication
This drug in indicated for the following conditions Label:
Major depressive disorder in adults 12
Management of neuropathic pain in adults
Prophylactic treatment of chronic tension-type headache (CTTH) in adults
Prophylactic treatment of migraine in adults
Treatment of nocturnal enuresis in children aged 6 years and above when organic pathology, including spina bifida and related disorders, have been excluded and no response has been achieved to all other non-drug and drug treatments, including antispasmodics and vasopressin-related products. This product should only be prescribed by a healthcare professional with expertise in the management of persistent enuresis Label
Off-label uses: irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation, fibromyalgia, and insomnia
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Adhd ••• ••••• Treatment of Acute depression •••••••••••• Management of Anorexia nervosa ••• ••••• Management of Bulimia ••• ••••• Treatment of Depression •••••••••••• - Contraindications & Blackbox Warnings
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Effects in pain and depression
Amitriptyline is a tricyclic antidepressant and an analgesic. It has anticholinergic and sedative properties Label. Clinical studies have shown that oral amitriptyline achieves, at a minimum, good to moderate response in up to 2/3 of patients diagnosed with post-herpetic neuralgia and 3/4 of patients diagnosed with diabetic neuropathic pain, and neurogenic pain syndromes that are frequently unresponsive to narcotic analgesics. Amitriptyline has also shown efficacy in diverse groups of patients with chronic non-malignant pain. There have also been some studies showing efficacy in managing fibromyalgia (an off-label use of this drug) 5, 8.
Cardiovascular and Anticholinergic Effects
Amitriptyline has strong anticholinergic properties and may cause ECG changes and quinidine-like effects on the heart 13. Amitriptyline may inhibit ion channels, which are necessary for cardiac repolarization (hERG channels), in the upper micromolar range of therapeutic plasma concentrations. Therefore, amitriptyline may increase the risk for cardiac arrhythmia Label. Orthostatic hypotension and tachycardia can be a problem in elderly patients receiving this drug at normal doses for depression. There is evidence in the literature that these effects may occur, rarely, at the lower dosages utilized in the treatment of pain. As with any other tricyclic antidepressant agent, increased glucose levels can occur with amitriptyline 6.
Effects on seizure threshold
This drug also decreases the convulsive threshold and causes alterations in EEG and sleep patterns 13.
- Mechanism of action
The mechanism of action of this drug is not fully elucidated. It is suggested that amitriptyline inhibits the membrane pump mechanism responsible for the re-uptake of transmitter amines, such as norepinephrine and serotonin, thereby increasing their concentration at the synaptic clefts of the brain Label, 10. These amines are important in regulating mood. The monoamine hypothesis in depression, one of the oldest hypotheses, postulates that deficiencies of serotonin (5-HT) and/or norepinephrine (NE) neurotransmission in the brain lead to depressive effects 9. This drug counteracts these mechanisms, and this may be the mechanism of amitriptyline in improving depressive symptoms.
Whether its analgesic effects are related to its mood-altering activities or attributable to a different, less obvious pharmacological action (or a combination of both) is unknown 6.
- Absorption
Rapidly absorbed following oral administration (bioavailability is 30-60% due to first pass metabolism). Peak plasma concentrations are reached 2-12 hours after oral or intramuscular administration Label. Steady-state plasma concentrations vary greatly and this variation may be due to genetic differences 13.
- Volume of distribution
The apparent volume of distribution (Vd)β estimated after intravenous administration is 1221 L±280 L; range 769-1702 L (16±3 L/kg) Label. It is found widely distributed throughout the body 6. Amitriptyline and the main metabolite nortriptyline pass across the placental barrier and small amounts are present in breast milk Label.
- Protein binding
Very highly protein bound (95%) in plasma and tissues Label.
- Metabolism
In vitro, the metabolism of amitriptyline occurs mainly by demethylation (CYP2C19, CYP3A4) as well as hydroxylation (CYP2D6) followed by conjugation with glucuronic acid. Other isozymes involved in amitriptyline metabolism are CYP1A2 and CYP2C9. The metabolism of this drug is subject to genetic polymorphisms. The main active metabolite is the secondary amine, nortriptyline Label.
Nortriptyline is a stronger inhibitor of noradrenaline than of serotonin uptake, while amitriptyline inhibits the uptake of noradrenaline and serotonin with equal efficacy. Other metabolites such as cis- and trans-10-hydroxyamitriptyline and cis- and trans-10-hydroxynortriptyline have the same pharmacologic profile as nortriptyline but are significantly weaker. Demethylnortriptyline and amitriptyline N oxide are only present in plasma in negligible amounts; the latter is mostly inactive Label.
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- Route of elimination
Amitriptyline and its metabolites are mainly excreted in the urine. Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with approximately 2% of unchanged drug appearing in the urine Label. 25-50% of a single orally administered dose is excreted in urine as inactive metabolites within 24 hours Label. Small amounts are excreted in feces via biliary elimination 13.
- Half-life
The elimination half-life (t1⁄2 β) amitriptyline after peroral administration is about 25 hours (24.65 ± 6.31 hours; range 16.49-40.36 hours) Label.
- Clearance
The mean systemic clearance (Cls) is 39.24 ± 10.18 L/h (range: 24.53-53.73 L/h) Label. No clear effect of older age on the pharmacokinetics of amitriptyline has been determined, although it is possible that clearance may be decreased 6.
- Adverse Effects
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Toxicity Data: Oral TDLO (child): 4167 μg/kg; Oral TDLO (man): 714 μg/kg/1D (intermittent); Oral TDLO (woman): 10 mg/kg 13.
Ingestion of 750 mg or more by an adult may result in severe toxicity. The effects in overdose are further increased by simultaneous ingestion of alcohol and another psychotropic agent Label. Symptoms of overdose include abnormally low blood pressure, confusion, convulsions, dilated pupils and other eye problems, disturbed concentration, drowsiness, hallucinations, impaired heart function, rapid or irregular heartbeat, reduced body temperature, stupor, and unresponsiveness or coma, among others Label, 13.
Use in pregnancy
For amitriptyline, only limited clinical data are available regarding its use in pregnancy. Amitriptyline is not recommended during pregnancy unless clearly required and only after careful consideration of both risks and benefits Label.
Use in breastfeeding
Amitriptyline and its metabolites are excreted into breast milk (corresponding to 0.6 % - 1 % of the maternal dose). A risk to the suckling child must be considered. A decision should be made as to whether it is appropriate to discontinue breastfeeding or to discontinue/abstain from the therapy of this medicinal product, considering the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Effects on fertility
Animal studies have shown reproductive toxicity. No data on the effects of amitriptyline on human fertility are available Label.
Mutagenesis and carcinogenesis
The genotoxic potential of amitriptyline has been investigated in various in vitro and in vivo studies. Although these investigations showed some contradictory results, a potential of amitriptyline to lead to chromosome abnormalities cannot be excluded. Long-term carcinogenicity studies have not been performed to this date Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2D6 CYP2D6*4 (A;A) A Allele Effect Directly Studied Patients with this genotype have reduced metabolism of amitriptyline. Details Multidrug resistance protein 1 --- (C;C) / (C;T) C Allele Effect Directly Studied Patients with this genotype have an increased likelihood of remission when using amitriptyline to treat major depressive disorder Details Cytochrome P450 2C19 CYP2C19*2 (A;A) / (A;G) G > A Directly Studied Effect Patients with this genotype have reduced metabolism of amitriptyline. Details Multidrug resistance protein 1 --- (C;C) / (C;T) T > C Effect Directly Studied Patients with this genotype have increased risk of adverse events with amitriptyline Details Cytochrome P450 2D6 CYP2D6*3 Not Available 2549delA Effect Directly Studied The presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of amitriptyline. Details Cytochrome P450 2D6 CYP2D6*4 Not Available A allele Effect Directly Studied The presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of amitriptyline. Details Cytochrome P450 2D6 CYP2D6*5 Not Available Whole-gene deletion Effect Directly Studied The presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of amitriptyline. Details Cytochrome P450 2D6 CYP2D6*6 Not Available 1707delT Effect Directly Studied The presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of amitriptyline. Details Cytochrome P450 2C19 CYP2C19*2 Not Available 681G>A Effect Directly Studied The presence of this polymorphism in CYP2C19 is associated with poor metabolism of amitriptyline. Details Cytochrome P450 2C19 CYP2C19*3 Not Available 636G>A Effect Directly Studied The presence of this polymorphism in CYP2C19 is associated with reduced or poor metabolism of amitriptyline. Details Cytochrome P450 2D6 CYP2D6*7 Not Available 2935A>C Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*8 Not Available 1758G>T Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*11 Not Available 883G>C Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*12 Not Available 124G>A Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*13 Not Available CYP2D7/2D6 hybrid gene structure Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*14A Not Available 1758G>A Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*15 Not Available 137insT, 137_138insT Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*19 Not Available 2539_2542delAACT Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*20 Not Available 1973_1974insG Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*21 Not Available 2573insC Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*31 Not Available -1770G>A / -1584C>G … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*36 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*38 Not Available 2587_2590delGACT Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*40 Not Available 1863_1864ins(TTT CGC CCC)2 Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*42 Not Available 3259_3260insGT Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*44 Not Available 2950G>C Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*47 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*51 Not Available -1584C>G / -1235A>G … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*56 Not Available 3201C>T Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*57 Not Available 100C>T / 310G>T … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*62 Not Available 4044C>T Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*68A Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*68B Not Available Similar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4. Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*69 Not Available 2988G>A / -1426C>T … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*92 Not Available 1995delC Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*100 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*101 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*2A Not Available 681G>A Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*2B Not Available 681G>A Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*4 Not Available 1A>G Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*5 Not Available 1297C>T Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*6 Not Available 395G>A Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*7 Not Available 19294T>A Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*22 Not Available 557G>C / 991A>G Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*24 Not Available 99C>T / 991A>G … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*35 Not Available 12662A>G Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*3 Not Available C allele Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*5 Not Available Whole-gene deletion Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*6 Not Available 1707delT Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*7 Not Available 2935A>C Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*8 Not Available 1758G>T Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*11 Not Available 883G>C Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*12 Not Available 124G>A Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*13 Not Available CYP2D7/2D6 hybrid gene structure Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*14A Not Available 1758G>A Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*15 Not Available 137insT, 137_138insT Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*19 Not Available 2539_2542delAACT Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*20 Not Available 1973_1974insG Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*21 Not Available 2573insC Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*31 Not Available -1770G>A / -1584C>G … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*36 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*38 Not Available 2587_2590delGACT Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*40 Not Available 1863_1864ins(TTT CGC CCC)2 Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*42 Not Available 3259_3260insGT Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*44 Not Available 2950G>C Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*47 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*51 Not Available -1584C>G / -1235A>G … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*56 Not Available 3201C>T Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*57 Not Available 100C>T / 310G>T … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*62 Not Available 4044C>T Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*68A Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*68B Not Available Similar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4. Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*69 Not Available 2988G>A / -1426C>T … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*92 Not Available 1995delC Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*100 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*101 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2C19 CYP2C19*2A Not Available 681G>A ADR Inferred Those with the AA or AG genotype are poor metabolizers of amitriptyline Details Cytochrome P450 2C19 CYP2C19*2B Not Available 681G>A ADR Inferred Those with the AA or AG genotype are poor metabolizers of amitriptyline Details Cytochrome P450 2C19 CYP2C19*3 Not Available 636G>A ADR Inferred Those with the AA or AG genotype are poor metabolizers of amitriptyline Details Cytochrome P450 2C19 CYP2C19*4 Not Available 1A>G ADR Inferred Those with the AA or AG genotype are poor metabolizers of amitriptyline Details Cytochrome P450 2C19 CYP2C19*5 Not Available 1297C>T ADR Inferred Those with the AA or AG genotype are poor metabolizers of amitriptyline Details Cytochrome P450 2C19 CYP2C19*6 Not Available 395G>A ADR Inferred Those with the AA or AG genotype are poor metabolizers of amitriptyline Details Cytochrome P450 2C19 CYP2C19*7 Not Available 19294T>A ADR Inferred Those with the AA or AG genotype are poor metabolizers of amitriptyline Details Cytochrome P450 2C19 CYP2C19*22 Not Available 557G>C / 991A>G ADR Inferred Those with the AA or AG genotype are poor metabolizers of amitriptyline Details Cytochrome P450 2C19 CYP2C19*24 Not Available 99C>T / 991A>G … show all ADR Inferred Those with the AA or AG genotype are poor metabolizers of amitriptyline Details Cytochrome P450 2C19 CYP2C19*35 Not Available 12662A>G ADR Inferred Those with the AA or AG genotype are poor metabolizers of amitriptyline Details Cytochrome P450 2D6 CYP2D6*3 Not Available G allele Effect Directly Studied The presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of amitriptyline. Details Cytochrome P450 2D6 CYP2D6*4 Not Available 3877G>A Effect Directly Studied The presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of amitriptyline. Details
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Amitriptyline is combined with 1,2-Benzodiazepine. Abacavir The metabolism of Abacavir can be decreased when combined with Amitriptyline. Abametapir The serum concentration of Amitriptyline can be increased when it is combined with Abametapir. Abatacept The metabolism of Amitriptyline can be increased when combined with Abatacept. Abiraterone The metabolism of Amitriptyline can be decreased when combined with Abiraterone. - Food Interactions
- Avoid alcohol.
- Avoid St. John's Wort.
- Limit caffeine intake.
- Take with food. Food reduces irritation.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Amitriptyline hydrochloride 26LUD4JO9K 549-18-8 KFYRPLNVJVHZGT-UHFFFAOYSA-N Amitriptyline pamoate YX6VNM127F 17086-03-2 HBFZQWHVSYYTGA-UHFFFAOYSA-N - Product Images
- International/Other Brands
- Adepril (Teofarma) / Amitryp (Raza) / Conmitrip (Condrugs) / Endep (Alphapharm) / Fiorda (Driburg) / Kamitrin (Saga) / Laroxyl (Deva) / Latilin (La Pharmaceuticals) / Maxitrip (Invision) / Redomex (Lundbeck) / Saroten (Lundbeck) / Sarotex (Lundbeck) / Sarotex Retard (Lundbeck) / Syneudon (Krewel Meuselbach) / Tryptanol (Merck Sharp & Dohme) / Tryptizol (Algorithm) / Uxen Retard (Sanofi-Aventis)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Amitriptyline Tablet 10 mg Oral Sanis Health Inc Not applicable Not applicable Canada 
Amitriptyline Tablet 10 mg Oral Sivem Pharmaceuticals Ulc 2016-02-11 2018-12-05 Canada Amitriptyline Tablet 50 mg Oral Sanis Health Inc Not applicable Not applicable Canada Amitriptyline Tablet 50 mg Oral Sivem Pharmaceuticals Ulc 2016-02-11 2018-11-01 Canada Amitriptyline Tablet 25 mg Oral Sanis Health Inc Not applicable Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ag-amitriptyline Tablet 10 mg Oral Angita Pharma Inc. 2018-12-24 Not applicable Canada Ag-amitriptyline Tablet 50 mg Oral Angita Pharma Inc. 2018-12-24 Not applicable Canada Ag-amitriptyline Tablet 75 mg Oral Angita Pharma Inc. Not applicable Not applicable Canada Ag-amitriptyline Tablet 25 mg Oral Angita Pharma Inc. 2018-12-24 Not applicable Canada Amitriptyline HCL Tablet, film coated 25 mg/1 Oral Advanced Rx Pharmacy of Tennessee, LLC 2023-03-22 Not applicable US 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Apo Peram Tab 2-25 Amitriptyline hydrochloride (25 mg) + Perphenazine (2 mg) Tablet Oral Apotex Corporation 1977-12-31 2011-08-05 Canada Apo Peram Tab 3-15 Amitriptyline hydrochloride (15 mg) + Perphenazine (3 mg) Tablet Oral Apotex Corporation 1977-12-31 2011-08-05 Canada Chlordiazepoxide and Amitriptyline HCl Amitriptyline hydrochloride (12.5 mg/1) + Chlordiazepoxide (5 mg/1) Tablet Oral Par Pharmaceutical 1988-05-09 1999-07-16 US Chlordiazepoxide and Amitriptyline HCl Amitriptyline hydrochloride (25 mg/1) + Chlordiazepoxide (10 mg/1) Tablet Oral Par Pharmaceutical 1988-05-09 1999-07-16 US Chlordiazepoxide and Amitriptyline Hydrochloride Amitriptyline hydrochloride (27.98 mg/1) + Chlordiazepoxide (10 mg/1) Tablet, film coated Oral Mylan Pharmaceuticals Inc. 1986-12-10 Not applicable US 
- Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Equipto - Amitriptyline External Cream Compounding Kit Amitriptyline hydrochloride (1 g/2.4g) Kit Topical Alvix Laboratories 2015-01-20 2018-03-08 US Sentravil PM-25 Amitriptyline hydrochloride (25 mg/1) + Choline (250 mg/1) Kit Oral Physician Therapeutics Llc 2011-07-07 Not applicable US Zyvodol Amitriptyline hydrochloride (4 g/4g) + Diclofenac sodium (3 g/3g) + Lidocaine hydrochloride (2.5 g/2.5g) + Prilocaine hydrochloride (2.5 g/2.5g) Kit Topical Accumix Pharmaceuticals 2014-12-15 2015-07-17 US
Categories
- ATC Codes
- N06AA09 — Amitriptyline
- N06AA — Non-selective monoamine reuptake inhibitors
- N06A — ANTIDEPRESSANTS
- N06 — PSYCHOANALEPTICS
- N — NERVOUS SYSTEM
- Drug Categories
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- Adrenergic Antagonists
- Adrenergic Uptake Inhibitors
- Agents producing tachycardia
- Agents that produce hypertension
- Agents that reduce seizure threshold
- Analgesics
- Analgesics, Non-Narcotic
- Anticholinergic Agents
- Antidepressive Agents
- Antidepressive Agents Indicated for Depression
- Antidepressive Agents, Tricyclic
- Central Nervous System Agents
- Central Nervous System Depressants
- Combined Inhibitors of Serotonin/Norepinephrine Reuptake
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (moderate)
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Histamine Antagonists
- Histamine H1 Antagonists
- Membrane Transport Modulators
- Moderate Risk QTc-Prolonging Agents
- Muscarinic Antagonists
- Narrow Therapeutic Index Drugs
- Neurotoxic agents
- Neurotransmitter Agents
- Neurotransmitter Uptake Inhibitors
- Non-Selective Monoamine Reuptake Inhibitors
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Psychotropic Drugs
- QTc Prolonging Agents
- Sensory System Agents
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin 5-HT2C Receptor Antagonists
- Serotonin Agents
- Serotonin Modulators
- Serotonin Receptor Antagonists
- Tertiary amine tricyclic antidepressants
- Tricyclics and Other Norepinephrine-reuptake Inhibitors
- UGT1A1 Inhibitors
- UGT1A4 substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dibenzocycloheptenes. These are compounds containing a dibenzocycloheptene moiety, which consists of two benzene rings connected by a cycloheptene ring.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Dibenzocycloheptenes
- Sub Class
- Not Available
- Direct Parent
- Dibenzocycloheptenes
- Alternative Parents
- Trialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Amine / Aromatic homopolycyclic compound / Dibenzocycloheptene / Hydrocarbon derivative / Organic nitrogen compound / Organonitrogen compound / Organopnictogen compound / Tertiary aliphatic amine / Tertiary amine
- Molecular Framework
- Aromatic homopolycyclic compounds
- External Descriptors
- tertiary amine, organic tricyclic compound (CHEBI:2666)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 1806D8D52K
- CAS number
- 50-48-6
- InChI Key
- KRMDCWKBEZIMAB-UHFFFAOYSA-N
- InChI
- InChI=1S/C20H23N/c1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20/h3-6,8-12H,7,13-15H2,1-2H3
- IUPAC Name
- dimethyl(3-{tricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene}propyl)amine
- SMILES
- CN(C)CCC=C1C2=CC=CC=C2CCC2=CC=CC=C12
References
- Synthesis Reference
Manfred Durr, Benedikt Gajdos, Klaus-Dieter Gneuss, Ekkehard Harhausen, Jurgen Seidel, "Pharmaceutical amitriptylin oxide preparation and process for its manufacture." U.S. Patent US4567202, issued January 28, 1986.
US4567202- General References
- Otaka M, Jin M, Odashima M, Matsuhashi T, Wada I, Horikawa Y, Komatsu K, Ohba R, Oyake J, Hatakeyama N, Watanabe S: New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline. Aliment Pharmacol Ther. 2005 Jun;21 Suppl 2:42-6. [Article]
- Hisaoka K, Tsuchioka M, Yano R, Maeda N, Kajitani N, Morioka N, Nakata Y, Takebayashi M: Tricyclic antidepressant amitriptyline activates fibroblast growth factor receptor signaling in glial cells: involvement in glial cell line-derived neurotrophic factor production. J Biol Chem. 2011 Jun 17;286(24):21118-28. doi: 10.1074/jbc.M111.224683. Epub 2011 Apr 22. [Article]
- Yan L, Wang Q, Fu Q, Ye Q, Xiao H, Wan Q: Amitriptyline inhibits currents and decreases the mRNA expression of voltage-gated sodium channels in cultured rat cortical neurons. Brain Res. 2010 Jun 8;1336:1-9. doi: 10.1016/j.brainres.2010.04.016. Epub 2010 Apr 14. [Article]
- Olesen OV, Linnet K: Metabolism of the tricyclic antidepressant amitriptyline by cDNA-expressed human cytochrome P450 enzymes. Pharmacology. 1997 Nov;55(5):235-43. doi: 10.1159/000139533. [Article]
- Lawson K: A Brief Review of the Pharmacology of Amitriptyline and Clinical Outcomes in Treating Fibromyalgia. Biomedicines. 2017 May 17;5(2). pii: biomedicines5020024. doi: 10.3390/biomedicines5020024. [Article]
- Bryson HM, Wilde MI: Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states. Drugs Aging. 1996 Jun;8(6):459-76. doi: 10.2165/00002512-199608060-00008. [Article]
- Guaiana G, Barbui C, Hotopf M: Amitriptyline versus other types of pharmacotherapy for depression. Cochrane Database Syst Rev. 2003;(2):CD004186. doi: 10.1002/14651858.CD004186 . [Article]
- Nishishinya B, Urrutia G, Walitt B, Rodriguez A, Bonfill X, Alegre C, Darko G: Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy. Rheumatology (Oxford). 2008 Dec;47(12):1741-6. doi: 10.1093/rheumatology/ken317. Epub 2008 Aug 12. [Article]
- Moret C, Briley M: The importance of norepinephrine in depression. Neuropsychiatr Dis Treat. 2011;7(Suppl 1):9-13. doi: 10.2147/NDT.S19619. Epub 2011 May 31. [Article]
- Gupta SK, Shah JC, Hwang SS: Pharmacokinetic and pharmacodynamic characterization of OROS and immediate-release amitriptyline. Br J Clin Pharmacol. 1999 Jul;48(1):71-8. [Article]
- Fangmann P, Assion HJ, Juckel G, Gonzalez CA, Lopez-Munoz F: Half a century of antidepressant drugs: on the clinical introduction of monoamine oxidase inhibitors, tricyclics, and tetracyclics. Part II: tricyclics and tetracyclics. J Clin Psychopharmacol. 2008 Feb;28(1):1-4. doi: 10.1097/jcp.0b013e3181627b60. [Article]
- DailyMed Label: ELAVIL (amitriptyline) Oral Tablets [Link]
- Elavil Monograph [File]
- Safety data sheet, amitriptyline [File]
- External Links
- Human Metabolome Database
- HMDB0014466
- KEGG Drug
- D07448
- KEGG Compound
- C06824
- PubChem Compound
- 2160
- PubChem Substance
- 46508798
- ChemSpider
- 2075
- BindingDB
- 50020712
- 704
- ChEBI
- 2666
- ChEMBL
- CHEMBL629
- ZINC
- ZINC000000968257
- Therapeutic Targets Database
- DNC001466
- PharmGKB
- PA448385
- Guide to Pharmacology
- GtP Drug Page
- PDBe Ligand
- TP0
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Amitriptyline
- PDB Entries
- 3apv / 5ha9
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Depressive Disorder 1 4 Completed Supportive Care Cerebral Palsy (CP) / Excessive crying / Pain 1 4 Completed Treatment Anxiety Disorders / Moods Disorders / Schizophrenia 1 4 Completed Treatment Chronic Pain 2 4 Completed Treatment Diarrhoea Predominant Irritable Bowel Syndrome 1
Pharmacoeconomics
- Manufacturers
- Hoffmann la roche inc
- Watson laboratories inc
- Astrazeneca pharmaceuticals lp
- Bristol myers squibb co
- Warner chilcott div warner lambert co
- American therapeutics inc
- Caraco pharmaceutical laboratories ltd
- Copley pharmaceutical inc
- Halsey drug co inc
- Lederle laboratories div american cyanamid co
- Mutual pharmaceutical co inc
- Mylan pharmaceuticals inc
- Par pharmaceutical inc
- Pliva inc
- Purepac pharmaceutical co
- Roxane laboratories inc
- Sandoz inc
- Superpharm corp
- Teva pharmaceuticals usa inc
- Ucb inc
- Usl pharma inc
- Vangard laboratories inc div midway medical co
- Vintage pharmaceuticals inc
- West ward pharmaceutical corp
- Packagers
- 4uOrtho LLC
- Advanced Pharmaceutical Services Inc.
- Amerisource Health Services Corp.
- Apotheca Inc.
- A-S Medication Solutions LLC
- Blenheim Pharmacal
- Bryant Ranch Prepack
- Caraco Pharmaceutical Labs
- Cardinal Health
- Caremark LLC
- Comprehensive Consultant Services Inc.
- Corepharma LLC
- Coupler Enterprises Inc.
- DHHS Program Support Center Supply Service Center
- Direct Dispensing Inc.
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- Group Health Cooperative
- H.J. Harkins Co. Inc.
- Heartland Repack Services LLC
- Innoviant Pharmacy Inc.
- Kaiser Foundation Hospital
- Keltman Pharmaceuticals Inc.
- Lake Erie Medical and Surgical Supply
- Legacy Pharmaceuticals Packaging LLC
- Liberty Pharmaceuticals
- Major Pharmaceuticals
- Medisca Inc.
- Medvantx Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Mutual Pharmaceutical Co.
- Mylan
- Nanjing Famu Chemicals Co. Ltd.
- Neuman Distributors Inc.
- Nucare Pharmaceuticals Inc.
- Palmetto Pharmaceuticals Inc.
- PCA LLC
- PD-Rx Pharmaceuticals Inc.
- Pharmedix
- Pharmpak Inc.
- Physicians Total Care Inc.
- Pliva Inc.
- Preferred Pharmaceuticals Inc.
- Prepackage Specialists
- Prepak Systems Inc.
- Prescript Pharmaceuticals
- Prescription Dispensing Service Inc.
- Qualitest
- Rebel Distributors Corp.
- Redpharm Drug
- Remedy Repack
- Sandhills Packaging Inc.
- Sandoz
- Southwood Pharmaceuticals
- St Mary's Medical Park Pharmacy
- Stat Rx Usa
- UDL Laboratories
- United Research Laboratories Inc.
- Va Cmop Dallas
- Valeant Ltd.
- Vangard Labs Inc.
- Vintage Pharmaceuticals Inc.
- Dosage Forms
Form Route Strength Solution Oral 10 mg Injection, solution Intramuscular 30 mg/3mL Pill Oral 10 MG Pill Oral 25 MG Tablet Oral Tablet, delayed release Oral 25 mg Tablet, film coated Oral 2500000 mg Tablet, coated Oral Capsule, extended release Oral 25 MG Capsule, extended release Oral 75 MG Tablet, film coated Oral 8.8 MG Tablet, film coated Oral 44.2 MG Tablet, film coated Oral 22.1 MG Tablet, film coated Oral 44.19 MG Tablet, film coated Oral 66.29 MG Tablet, film coated Oral 8.84 MG Tablet, film coated Oral 88.38 MG Tablet, film coated Oral 50 MG Tablet, extended release Oral 100 MG Solution Oral 40 mg/mL Tablet, film coated Oral 100 MG Tablet, film coated Oral 75 MG Tablet, film coated Oral Tablet Oral 10 mg/1 Tablet Oral 100 mg/1 Tablet Oral 150 mg/1 Tablet Oral 50 mg/1 Tablet Oral 75 mg/1 Tablet, coated Oral 25 mg/1 Tablet, film coated Oral 10 mg/1 Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 150 mg/1 Tablet, film coated Oral 25 mg/1 Tablet, film coated Oral 50 mg/1 Tablet, film coated Oral 75 mg/1 Tablet Oral 25 mg / tab Tablet Oral 25.000 mg Tablet, film coated Oral 10 mg Tablet, film coated Oral 25 mg Tablet Oral 10 mg Tablet Oral 50 mg Tablet Oral 75 mg Tablet Oral 25 mg/1 Syrup Oral 2 mg / mL Kit Topical 1 g/2.4g Injection Intramuscular 20 mg/2ml Injection Intramuscular 50 mg/2ml Solution / drops Oral 40 MG/ML Capsule Oral Tablet Oral 10 mg / tab Tablet Oral 50 mg / tab Tablet Oral 75 mg / tab Tablet Oral Tablet, film coated Oral Tablet Oral 100 mg Tablet, extended release Oral 75 MG Kit Oral Syrup Oral 200 mg Tablet Oral 28.300 mg Tablet, sugar coated Oral 10 mg Injection Intramuscular 10 mg/ml Kit Topical Tablet, sugar coated Oral 25 mg Tablet, sugar coated Oral 50 mg Tablet, coated Oral 10 mg Tablet, coated Oral 50 mg Tablet Oral 25 mg Tablet, coated Oral 25 mg Tablet, coated Oral - Prices
Unit description Cost Unit Amitriptyline hcl powder 7.34USD g Amitriptyline hcl 150 mg tablet 1.18USD tablet Amitriptyline hcl 100 mg tablet 0.66USD tablet Amitriptyline hcl 75 mg tablet 0.54USD tablet Apo-Amitriptyline 75 mg Tablet 0.38USD tablet Amitriptyline hcl 50 mg tablet 0.37USD tablet Amitriptyline hcl 10 mg tablet 0.3USD tablet Apo-Amitriptyline 50 mg Tablet 0.25USD tablet Amitriptyline hcl 25 mg tablet 0.21USD tablet Apo-Amitriptyline 25 mg Tablet 0.13USD tablet Apo-Amitriptyline 10 mg Tablet 0.07USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 196-197 https://www.chemicalbook.com/ChemicalProductProperty_US_CB1159271.aspx boiling point (°C) 410.26°C (rough estimate) https://www.chemicalbook.com/ChemicalProductProperty_US_CB1159271.aspx water solubility freely soluble in water https://pdf.hres.ca/dpd_pm/00043995.PDF logP 4.92 https://pdfs.semanticscholar.org/6fc5/ceca026da3b93fb450ece63df320b5597ca2.pdf logS -4.39 https://www.acdlabs.com/download/publ/2007/low_quality_predictions.pdf pKa 9.4 https://www.chemicalbook.com/ChemicalProductProperty_US_CB1159271.aspx - Predicted Properties
Property Value Source Water Solubility 0.0045 mg/mL ALOGPS logP 5.1 ALOGPS logP 4.81 Chemaxon logS -4.8 ALOGPS pKa (Strongest Basic) 9.76 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 3.24 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 101.51 m3·mol-1 Chemaxon Polarizability 33.74 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9941 Blood Brain Barrier + 0.9512 Caco-2 permeable + 0.8867 P-glycoprotein substrate Substrate 0.7567 P-glycoprotein inhibitor I Inhibitor 0.8563 P-glycoprotein inhibitor II Inhibitor 0.6447 Renal organic cation transporter Inhibitor 0.7955 CYP450 2C9 substrate Non-substrate 0.7826 CYP450 2D6 substrate Substrate 0.8918 CYP450 3A4 substrate Substrate 0.7501 CYP450 1A2 substrate Inhibitor 0.7324 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Inhibitor 0.8933 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.9158 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6955 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.8127 Biodegradation Not ready biodegradable 0.8727 Rat acute toxicity 2.9697 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7531 hERG inhibition (predictor II) Inhibitor 0.6767
Spectra
- Mass Spec (NIST)
- Download (7.48 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 180.648202 predictedDarkChem Lite v0.1.0 [M-H]- 180.922002 predictedDarkChem Lite v0.1.0 [M-H]- 162.05559 predictedDeepCCS 1.0 (2019) [M+H]+ 183.092402 predictedDarkChem Lite v0.1.0 [M+H]+ 182.984902 predictedDarkChem Lite v0.1.0 [M+H]+ 164.41359 predictedDeepCCS 1.0 (2019) [M+Na]+ 180.877802 predictedDarkChem Lite v0.1.0 [M+Na]+ 170.50673 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Norepinephrine:sodium symporter activity
- Specific Function
- Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name
- SLC6A2
- Uniprot ID
- P23975
- Uniprot Name
- Sodium-dependent noradrenaline transporter
- Molecular Weight
- 69331.42 Da
References
- Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. [Article]
- Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [Article]
- Bryson HM, Wilde MI: Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states. Drugs Aging. 1996 Jun;8(6):459-76. doi: 10.2165/00002512-199608060-00008. [Article]
- Elavil Monograph [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serotonin:sodium symporter activity
- Specific Function
- Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
- Gene Name
- SLC6A4
- Uniprot ID
- P31645
- Uniprot Name
- Sodium-dependent serotonin transporter
- Molecular Weight
- 70324.165 Da
References
- Gould GG, Altamirano AV, Javors MA, Frazer A: A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters. Biol Psychiatry. 2006 Mar 1;59(5):408-14. Epub 2005 Sep 2. [Article]
- Troelsen KB, Nielsen EO, Mirza NR: Chronic treatment with duloxetine is necessary for an anxiolytic-like response in the mouse zero maze: the role of the serotonin transporter. Psychopharmacology (Berl). 2005 Oct;181(4):741-50. Epub 2005 Sep 29. [Article]
- Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. [Article]
- Ushijima K, Sakaguchi H, Sato Y, To H, Koyanagi S, Higuchi S, Ohdo S: Chronopharmacological study of antidepressants in forced swimming test of mice. J Pharmacol Exp Ther. 2005 Nov;315(2):764-70. Epub 2005 Aug 3. [Article]
- Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [Article]
- Werling LL, Keller A, Frank JG, Nuwayhid SJ: A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp Neurol. 2007 Oct;207(2):248-57. Epub 2007 Jun 30. [Article]
- Bryson HM, Wilde MI: Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states. Drugs Aging. 1996 Jun;8(6):459-76. doi: 10.2165/00002512-199608060-00008. [Article]
- Elavil Monograph [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Virus receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
- Gene Name
- HTR2A
- Uniprot ID
- P28223
- Uniprot Name
- 5-hydroxytryptamine receptor 2A
- Molecular Weight
- 52602.58 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Pandey DK, Mahesh R, Kumar AA, Rao VS, Arjun M, Rajkumar R: A novel 5-HT(2A) receptor antagonist exhibits antidepressant-like effects in a battery of rodent behavioural assays: approaching early-onset antidepressants. Pharmacol Biochem Behav. 2010 Jan;94(3):363-73. doi: 10.1016/j.pbb.2009.09.018. Epub 2009 Oct 2. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- InhibitorInducer
- Curator comments
- Some studies suggest this receptor is upregulated by amitriptyline and some suggest it is down regulated by amitriptyline.
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
- Gene Name
- HTR1A
- Uniprot ID
- P08908
- Uniprot Name
- 5-hydroxytryptamine receptor 1A
- Molecular Weight
- 46106.335 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Rossi DV, Valdez M, Gould GG, Hensler JG: Chronic administration of venlafaxine fails to attenuate 5-HT1A receptor function at the level of receptor-G protein interaction. Int J Neuropsychopharmacol. 2006 Aug;9(4):393-406. doi: 10.1017/S1461145705005754. Epub 2005 Jul 22. [Article]
- Lesch KP, Disselkamp-Tietze J, Schmidtke A: 5-HT1A receptor function in depression: effect of chronic amitriptyline treatment. J Neural Transm Gen Sect. 1990;80(2):157-61. [Article]
- Jenck F, Moreau JL, Mutel V, Martin JR, Haefely WE: Evidence for a role of 5-HT1C receptors in the antiserotonergic properties of some antidepressant drugs. Eur J Pharmacol. 1993 Feb 9;231(2):223-9. doi: 10.1016/0014-2999(93)90453-o. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Opioid receptor activity
- Specific Function
- G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine n...
- Gene Name
- OPRD1
- Uniprot ID
- P41143
- Uniprot Name
- Delta-type opioid receptor
- Molecular Weight
- 40368.235 Da
References
- Onali P, Dedoni S, Olianas MC: Direct agonist activity of tricyclic antidepressants at distinct opioid receptor subtypes. J Pharmacol Exp Ther. 2010 Jan;332(1):255-65. doi: 10.1124/jpet.109.159939. Epub 2009 Oct 14. [Article]
- Benbouzid M, Gaveriaux-Ruff C, Yalcin I, Waltisperger E, Tessier LH, Muller A, Kieffer BL, Freund-Mercier MJ, Barrot M: Delta-opioid receptors are critical for tricyclic antidepressant treatment of neuropathic allodynia. Biol Psychiatry. 2008 Mar 15;63(6):633-6. doi: 10.1016/j.biopsych.2007.06.016. Epub 2007 Aug 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Opioid receptor activity
- Specific Function
- G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
- Gene Name
- OPRK1
- Uniprot ID
- P41145
- Uniprot Name
- Kappa-type opioid receptor
- Molecular Weight
- 42644.665 Da
References
- Onali P, Dedoni S, Olianas MC: Direct agonist activity of tricyclic antidepressants at distinct opioid receptor subtypes. J Pharmacol Exp Ther. 2010 Jan;332(1):255-65. doi: 10.1124/jpet.109.159939. Epub 2009 Oct 14. [Article]
- Carydakis C, Bourhim N, Giraud P, Cantau P, Oliver C, Castanas E: [Direct interaction of tricyclic antidepressants with opiate binding sites in the bovine adrenal medulla]. C R Acad Sci III. 1986;302(11):419-22. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- AgonistActivator
- General Function
- Transmembrane receptor protein tyrosine kinase activity
- Specific Function
- Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympatheti...
- Gene Name
- NTRK1
- Uniprot ID
- P04629
- Uniprot Name
- High affinity nerve growth factor receptor
- Molecular Weight
- 87496.465 Da
References
- Jang SW, Liu X, Chan CB, Weinshenker D, Hall RA, Xiao G, Ye K: Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Chem Biol. 2009 Jun 26;16(6):644-56. doi: 10.1016/j.chembiol.2009.05.010. [Article]
- Zheng X, Chen F, Zheng T, Huang F, Chen J, Tu W: Amitriptyline Activates TrkA to Aid Neuronal Growth and Attenuate Anesthesia-Induced Neurodegeneration in Rat Dorsal Root Ganglion Neurons. Medicine (Baltimore). 2016 May;95(18):e3559. doi: 10.1097/MD.0000000000003559. [Article]
- Rantamaki T, Vesa L, Antila H, Di Lieto A, Tammela P, Schmitt A, Lesch KP, Rios M, Castren E: Antidepressant drugs transactivate TrkB neurotrophin receptors in the adult rodent brain independently of BDNF and monoamine transporter blockade. PLoS One. 2011;6(6):e20567. doi: 10.1371/journal.pone.0020567. Epub 2011 Jun 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Protein homodimerization activity
- Specific Function
- Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differenti...
- Gene Name
- NTRK2
- Uniprot ID
- Q16620
- Uniprot Name
- BDNF/NT-3 growth factors receptor
- Molecular Weight
- 91998.175 Da
References
- Jang SW, Liu X, Chan CB, Weinshenker D, Hall RA, Xiao G, Ye K: Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Chem Biol. 2009 Jun 26;16(6):644-56. doi: 10.1016/j.chembiol.2009.05.010. [Article]
- Cai J, Hua F, Yuan L, Tang W, Lu J, Yu S, Wang X, Hu Y: Potential therapeutic effects of neurotrophins for acute and chronic neurological diseases. Biomed Res Int. 2014;2014:601084. doi: 10.1155/2014/601084. Epub 2014 Apr 9. [Article]
- O'Neill E, Kwok B, Day JS, Connor TJ, Harkin A: Amitriptyline protects against TNF-alpha-induced atrophy and reduction in synaptic markers via a Trk-dependent mechanism. Pharmacol Res Perspect. 2016 Mar 8;4(2):e00195. doi: 10.1002/prp2.195. eCollection 2016 Apr. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- AntagonistInhibitor
- General Function
- Protein heterodimerization activity
- Specific Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
- Gene Name
- ADRA1A
- Uniprot ID
- P35348
- Uniprot Name
- Alpha-1A adrenergic receptor
- Molecular Weight
- 51486.005 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Antagonist
- Curator comments
- This information is based on the results of in vitro studies. Data in the literature regarding this target are limited.
- General Function
- Alpha1-adrenergic receptor activity
- Specific Function
- This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
- Gene Name
- ADRA1D
- Uniprot ID
- P25100
- Uniprot Name
- Alpha-1D adrenergic receptor
- Molecular Weight
- 60462.205 Da
References
- Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [Article]
- RBCB PDB resource [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- AntagonistAgonist
- General Function
- Thioesterase binding
- Specific Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
- Gene Name
- ADRA2A
- Uniprot ID
- P08913
- Uniprot Name
- Alpha-2A adrenergic receptor
- Molecular Weight
- 48956.275 Da
References
- Ozdogan UK, Lahdesmaki J, Mansikka H, Scheinin M: Loss of amitriptyline analgesia in alpha 2A-adrenoceptor deficient mice. Eur J Pharmacol. 2004 Feb 6;485(1-3):193-6. [Article]
- Charney DS, Heninger GR, Sternberg DE: Alpha-2 adrenergic receptor sensitivity and the mechanism of action of antidepressant therapy. The effect of long-term amitriptyline treatment. Br J Psychiatry. 1983 Mar;142:265-75. [Article]
- Gray AM, Pache DM, Sewell RD: Do alpha2-adrenoceptors play an integral role in the antinociceptive mechanism of action of antidepressant compounds? Eur J Pharmacol. 1999 Aug 6;378(2):161-8. [Article]
- Cottingham C, Percival S, Birky T, Wang Q: Tricyclic antidepressants exhibit variable pharmacological profiles at the alpha(2A) adrenergic receptor. Biochem Biophys Res Commun. 2014 Aug 29;451(3):461-6. doi: 10.1016/j.bbrc.2014.08.024. Epub 2014 Aug 12. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Antagonist
- General Function
- Histamine receptor activity
- Specific Function
- In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
- Gene Name
- HRH1
- Uniprot ID
- P35367
- Uniprot Name
- Histamine H1 receptor
- Molecular Weight
- 55783.61 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Richelson E: Tricyclic antidepressants and histamine H1 receptors. Mayo Clin Proc. 1979 Oct;54(10):669-74. [Article]
- Kachur JF, Allbee WE, Gaginella TS: Antihistaminic and antimuscarinic effects of amitriptyline on guinea pig ileal electrolyte transport and muscle contractility in vitro. J Pharmacol Exp Ther. 1988 May;245(2):455-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- Data limited to in vitro study results.
- General Function
- Voltage-gated potassium channel activity
- Specific Function
- Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current...
- Gene Name
- KCNQ2
- Uniprot ID
- O43526
- Uniprot Name
- Potassium voltage-gated channel subfamily KQT member 2
- Molecular Weight
- 95846.575 Da
References
- Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Voltage-gated potassium channel activity
- Specific Function
- Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney (PubMed:1990381...
- Gene Name
- KCNA1
- Uniprot ID
- Q09470
- Uniprot Name
- Potassium voltage-gated channel subfamily A member 1
- Molecular Weight
- 56465.01 Da
References
- Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [Article]
- Freysoldt A, Fleckenstein J, Lang PM, Irnich D, Grafe P, Carr RW: Low concentrations of amitriptyline inhibit nicotinic receptors in unmyelinated axons of human peripheral nerve. Br J Pharmacol. 2009 Oct;158(3):797-805. doi: 10.1111/j.1476-5381.2009.00347.x. Epub 2009 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Blocker
- General Function
- Histamine receptor activity
- Specific Function
- The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and diff...
- Gene Name
- HRH2
- Uniprot ID
- P25021
- Uniprot Name
- Histamine H2 receptor
- Molecular Weight
- 40097.65 Da
References
- Angus JA, Black JW: Pharmacological assay of cardiac H2-receptor blockade by amitriptyline and lysergic acid diethylamide. Circ Res. 1980 Jun;46(6 Pt 2):I64-9. [Article]
- Traiffort E, Pollard H, Moreau J, Ruat M, Schwartz JC, Martinez-Mir MI, Palacios JM: Pharmacological characterization and autoradiographic localization of histamine H2 receptors in human brain identified with [125I]iodoaminopotentidine. J Neurochem. 1992 Jul;59(1):290-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Histamine receptor activity
- Specific Function
- The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agoni...
- Gene Name
- HRH4
- Uniprot ID
- Q9H3N8
- Uniprot Name
- Histamine H4 receptor
- Molecular Weight
- 44495.375 Da
References
- Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL, O'Dowd BF: Discovery of a novel member of the histamine receptor family. Mol Pharmacol. 2001 Mar;59(3):427-33. [Article]
- Connelly WM, Shenton FC, Lethbridge N, Leurs R, Waldvogel HJ, Faull RL, Lees G, Chazot PL: The histamine H4 receptor is functionally expressed on neurons in the mammalian CNS. Br J Pharmacol. 2009 May;157(1):55-63. doi: 10.1111/j.1476-5381.2009.00227.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Opioid receptor activity
- Specific Function
- Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma m...
- Gene Name
- SIGMAR1
- Uniprot ID
- Q99720
- Uniprot Name
- Sigma non-opioid intracellular receptor 1
- Molecular Weight
- 25127.52 Da
References
- Villard V, Meunier J, Chevallier N, Maurice T: Pharmacological interaction with the sigma1 (sigma1)-receptor in the acute behavioral effects of antidepressants. J Pharmacol Sci. 2011;115(3):279-92. [Article]
- Werling LL, Keller A, Frank JG, Nuwayhid SJ: A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp Neurol. 2007 Oct;207(2):248-57. Epub 2007 Jun 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
- Gene Name
- HTR2C
- Uniprot ID
- P28335
- Uniprot Name
- 5-hydroxytryptamine receptor 2C
- Molecular Weight
- 51820.705 Da
References
- Di Matteo V, De Blasi A, Di Giulio C, Esposito E: Role of 5-HT(2C) receptors in the control of central dopamine function. Trends Pharmacol Sci. 2001 May;22(5):229-32. [Article]
- Palvimaki EP, Roth BL, Majasuo H, Laakso A, Kuoppamaki M, Syvalahti E, Hietala J: Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor. Psychopharmacology (Berl). 1996 Aug;126(3):234-40. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- Curator comments
- This action is based on data from in vitro studies. Data in the literature are limited regarding this target action.
- General Function
- Protein heterodimerization activity
- Specific Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
- Gene Name
- ADRA1B
- Uniprot ID
- P35368
- Uniprot Name
- Alpha-1B adrenergic receptor
- Molecular Weight
- 56835.375 Da
References
- Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Serotonin receptor activity
- Specific Function
- This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
- Gene Name
- HTR7
- Uniprot ID
- P34969
- Uniprot Name
- 5-hydroxytryptamine receptor 7
- Molecular Weight
- 53554.43 Da
References
- Lucchelli A, Santagostino-Barbone MG, D'Agostino G, Masoero E, Tonini M: The interaction of antidepressant drugs with enteric 5-HT7 receptors. Naunyn Schmiedebergs Arch Pharmacol. 2000 Sep;362(3):284-9. [Article]
- Liu J, Reid AR, Sawynok J: Spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors, are involved in antinociception by systemically administered amitriptyline. Eur J Pharmacol. 2013 Jan 5;698(1-3):213-9. doi: 10.1016/j.ejphar.2012.10.042. Epub 2012 Nov 6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- Curator comments
- Data in the literature regarding this target are limited. These data are based on the results of in vitro studies.
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
- Gene Name
- HTR1D
- Uniprot ID
- P28221
- Uniprot Name
- 5-hydroxytryptamine receptor 1D
- Molecular Weight
- 41906.38 Da
References
- Werling LL, Keller A, Frank JG, Nuwayhid SJ: A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp Neurol. 2007 Oct;207(2):248-57. Epub 2007 Jun 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- Curator comments
- Data regarding this target action are limited in the literature.
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
- Gene Name
- OPRM1
- Uniprot ID
- P35372
- Uniprot Name
- Mu-type opioid receptor
- Molecular Weight
- 44778.855 Da
References
- Hamon M, Gozlan H, Bourgoin S, Benoliel JJ, Mauborgne A, Taquet H, Cesselin F, Mico JA: Opioid receptors and neuropeptides in the CNS in rats treated chronically with amoxapine or amitriptyline. Neuropharmacology. 1987 Jun;26(6):531-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- Curator comments
- Data are based on in vitro studies. There is limited information about this target action in the literature.
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
- Gene Name
- HTR1B
- Uniprot ID
- P28222
- Uniprot Name
- 5-hydroxytryptamine receptor 1B
- Molecular Weight
- 43567.535 Da
References
- Werling LL, Keller A, Frank JG, Nuwayhid SJ: A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp Neurol. 2007 Oct;207(2):248-57. Epub 2007 Jun 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- Curator comments
- Data based on in vitro studies. The information regarding this target in the literature is limited.
- General Function
- Serotonin receptor activity
- Specific Function
- This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
- Gene Name
- HTR6
- Uniprot ID
- P50406
- Uniprot Name
- 5-hydroxytryptamine receptor 6
- Molecular Weight
- 46953.625 Da
References
- Sebben M, Ansanay H, Bockaert J, Dumuis A: 5-HT6 receptors positively coupled to adenylyl cyclase in striatal neurones in culture. Neuroreport. 1994 Dec 20;5(18):2553-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Voltage-gated potassium channel activity
- Specific Function
- Probably important in the regulation of neuronal excitability. Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native ...
- Gene Name
- KCNQ3
- Uniprot ID
- O43525
- Uniprot Name
- Potassium voltage-gated channel subfamily KQT member 3
- Molecular Weight
- 96741.515 Da
References
- Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [Article]
- Syeda R, Santos JS, Montal M: The Sensorless Pore Module of Voltage-gated K+ Channel Family 7 Embodies the Target Site for the Anticonvulsant Retigabine. J Biol Chem. 2016 Feb 5;291(6):2931-7. doi: 10.1074/jbc.M115.683185. Epub 2015 Dec 1. [Article]
- Kind
- Protein
- Organism
- Rat
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
- Gene Name
- Htr2c
- Uniprot ID
- P08909
- Uniprot Name
- 5-hydroxytryptamine receptor 2C
- Molecular Weight
- 51916.005 Da
References
- Pithadia AB, Jain SM: 5-Hydroxytryptamine Receptor Subtypes and their Modulators with Therapeutic Potentials. J Clin Med Res. 2009 Jun;1(2):72-80. doi: 10.4021/jocmr2009.05.1237. Epub 2009 Jun 21. [Article]
- Jenck F, Moreau JL, Mutel V, Martin JR, Haefely WE: Evidence for a role of 5-HT1C receptors in the antiserotonergic properties of some antidepressant drugs. Eur J Pharmacol. 1993 Feb 9;231(2):223-9. doi: 10.1016/0014-2999(93)90453-o. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Ligand
- General Function
- Phosphatidylinositol phospholipase c activity
- Specific Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Components:
References
- Goldman P, Scranton T, Messer WS Jr: Interaction of amitriptyline with muscarinic receptor subtypes in the rat brain. Neurochem Int. 1989;14(4):447-54. [Article]
- Dilsaver SC, Snider RM, Alessi NE: Amitriptyline supersensitizes a central cholinergic mechanism. Biol Psychiatry. 1987 Apr;22(4):495-507. [Article]
- Snyder SH, Yamamura HI: Antidepressants and the muscarinic acetylcholine receptor. Arch Gen Psychiatry. 1977 Feb;34(2):236-9. [Article]
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Blocker
- General Function
- Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
- Specific Function
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Components:
| Name | UniProt ID |
|---|---|
| Potassium voltage-gated channel subfamily H member 2 | Q12809 |
| Potassium voltage-gated channel subfamily H member 6 | Q9H252 |
| Potassium voltage-gated channel subfamily H member 7 | Q9NS40 |
References
- Jo SH, Youm JB, Lee CO, Earm YE, Ho WK: Blockade of the HERG human cardiac K(+) channel by the antidepressant drug amitriptyline. Br J Pharmacol. 2000 Apr;129(7):1474-80. doi: 10.1038/sj.bjp.0703222. [Article]
- Teschemacher AG, Seward EP, Hancox JC, Witchel HJ: Inhibition of the current of heterologously expressed HERG potassium channels by imipramine and amitriptyline. Br J Pharmacol. 1999 Sep;128(2):479-85. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Baumann P: Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin Pharmacokinet. 1996 Dec;31(6):444-69. [Article]
- Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. doi: 10.1016/j.cbi.2008.02.001. Epub 2008 Feb 14. [Article]
- Ghahramani P, Ellis SW, Lennard MS, Ramsay LE, Tucker GT: Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997 Feb;43(2):137-44. [Article]
- Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. [Article]
- Yue QY, Sawe J: Different effects of inhibitors on the O- and N-demethylation of codeine in human liver microsomes. Eur J Clin Pharmacol. 1997;52(1):41-7. [Article]
- Flockhart Table of Drug Interactions [Link]
- Amitriptyline FDA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. doi: 10.1016/j.cbi.2008.02.001. Epub 2008 Feb 14. [Article]
- Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. [Article]
- Arici M, Ozhan G: The genetic profiles of CYP1A1, CYP1A2 and CYP2E1 enzymes as susceptibility factor in xenobiotic toxicity in Turkish population. Saudi Pharm J. 2017 Feb;25(2):294-297. doi: 10.1016/j.jsps.2016.06.001. Epub 2016 Jun 16. [Article]
- Zhou SF, Yang LP, Zhou ZW, Liu YH, Chan E: Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2. AAPS J. 2009 Sep;11(3):481-94. doi: 10.1208/s12248-009-9127-y. Epub 2009 Jul 10. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Shin JG, Park JY, Kim MJ, Shon JH, Yoon YR, Cha IJ, Lee SS, Oh SW, Kim SW, Flockhart DA: Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin. Drug Metab Dispos. 2002 Oct;30(10):1102-7. [Article]
- Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. [Article]
- Ryu S, Park S, Lee JH, Kim YR, Na HS, Lim HS, Choi HY, Hwang IY, Lee JG, Park ZW, Oh WY, Kim JM, Choi SE: A Study on CYP2C19 and CYP2D6 Polymorphic Effects on Pharmacokinetics and Pharmacodynamics of Amitriptyline in Healthy Koreans. Clin Transl Sci. 2017 Mar;10(2):93-101. doi: 10.1111/cts.12451. Epub 2017 Mar 14. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Ghahramani P, Ellis SW, Lennard MS, Ramsay LE, Tucker GT: Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997 Feb;43(2):137-44. [Article]
- Attia TZ, Yamashita T, Hammad MA, Hayasaki A, Sato T, Miyamoto M, Yasuhara Y, Nakamura T, Kagawa Y, Tsujino H, Omar MA, Abdelmageed OH, Derayea SM, Uno T: Effect of cytochrome P450 2C19 and 2C9 amino acid residues 72 and 241 on metabolism of tricyclic antidepressant drugs. Chem Pharm Bull (Tokyo). 2014;62(2):176-81. [Article]
- Olesen OV, Linnet K: Metabolism of the tricyclic antidepressant amitriptyline by cDNA-expressed human cytochrome P450 enzymes. Pharmacology. 1997 Nov;55(5):235-43. doi: 10.1159/000139533. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. doi: 10.1016/j.cbi.2008.02.001. Epub 2008 Feb 14. [Article]
- Ghahramani P, Ellis SW, Lennard MS, Ramsay LE, Tucker GT: Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997 Feb;43(2):137-44. [Article]
- Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Data based on in vitro studies. There are limited data in the literature regarding this enzyme action.
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. doi: 10.1016/j.cbi.2008.02.001. Epub 2008 Feb 14. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. [Article]
- Ekins S, Iyer M, Krasowski MD, Kharasch ED: Molecular characterization of CYP2B6 substrates. Curr Drug Metab. 2008 Jun;9(5):363-73. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. [Article]
- Martinez C, Garcia-Martin E, Blanco G, Gamito FJ, Ladero JM, Agundez JA: The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)-ibuprofen enantiomer in healthy subjects. Br J Clin Pharmacol. 2005 Jan;59(1):62-9. doi: 10.1111/j.1365-2125.2004.02183.x. [Article]
- Naraharisetti SB, Lin YS, Rieder MJ, Marciante KD, Psaty BM, Thummel KE, Totah RA: Human liver expression of CYP2C8: gender, age, and genotype effects. Drug Metab Dispos. 2010 Jun;38(6):889-93. doi: 10.1124/dmd.109.031542. Epub 2010 Feb 26. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- General Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
- Specific Function
- Glucuronosyltransferase activity
- Gene Name
- UGT2B10
- Uniprot ID
- P36537
- Uniprot Name
- UDP-glucuronosyltransferase 2B10
- Molecular Weight
- 60773.485 Da
References
- Kato Y, Izukawa T, Oda S, Fukami T, Finel M, Yokoi T, Nakajima M: Human UDP-glucuronosyltransferase (UGT) 2B10 in drug N-glucuronidation: substrate screening and comparison with UGT1A3 and UGT1A4. Drug Metab Dispos. 2013 Jul;41(7):1389-97. doi: 10.1124/dmd.113.051565. Epub 2013 Apr 23. [Article]
- Zhou D, Guo J, Linnenbach AJ, Booth-Genthe CL, Grimm SW: Role of human UGT2B10 in N-glucuronidation of tricyclic antidepressants, amitriptyline, imipramine, clomipramine, and trimipramine. Drug Metab Dispos. 2010 May;38(5):863-70. doi: 10.1124/dmd.109.030981. Epub 2010 Feb 4. [Article]
- Pattanawongsa A, Nair PC, Rowland A, Miners JO: Human UDP-Glucuronosyltransferase (UGT) 2B10: Validation of Cotinine as a Selective Probe Substrate, Inhibition by UGT Enzyme-Selective Inhibitors and Antidepressant and Antipsychotic Drugs, and Structural Determinants of Enzyme Inhibition. Drug Metab Dispos. 2016 Mar;44(3):378-88. doi: 10.1124/dmd.115.068213. Epub 2015 Dec 15. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Protein homodimerization activity
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A4
- Uniprot ID
- P22310
- Uniprot Name
- UDP-glucuronosyltransferase 1-4
- Molecular Weight
- 60024.535 Da
References
- Kato Y, Izukawa T, Oda S, Fukami T, Finel M, Yokoi T, Nakajima M: Human UDP-glucuronosyltransferase (UGT) 2B10 in drug N-glucuronidation: substrate screening and comparison with UGT1A3 and UGT1A4. Drug Metab Dispos. 2013 Jul;41(7):1389-97. doi: 10.1124/dmd.113.051565. Epub 2013 Apr 23. [Article]
- Zhou D, Guo J, Linnenbach AJ, Booth-Genthe CL, Grimm SW: Role of human UGT2B10 in N-glucuronidation of tricyclic antidepressants, amitriptyline, imipramine, clomipramine, and trimipramine. Drug Metab Dispos. 2010 May;38(5):863-70. doi: 10.1124/dmd.109.030981. Epub 2010 Feb 4. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Glutathione transferase activity
- Specific Function
- Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Components:
References
- Dalmizrak O, Kulaksiz-Erkmen G, Ozer N: The inhibition characteristics of human placental glutathione S-transferase-pi by tricyclic antidepressants: amitriptyline and clomipramine. Mol Cell Biochem. 2011 Sep;355(1-2):223-31. doi: 10.1007/s11010-011-0858-6. Epub 2011 May 13. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Brinkschulte M, Breyer-Pfaff U: The contribution of alpha 1-acid glycoprotein, lipoproteins, and albumin to the plasma binding of perazine, amitriptyline, and nortriptyline in healthy man. Naunyn Schmiedebergs Arch Pharmacol. 1980 Oct;314(1):61-6. doi: 10.1007/bf00498432. [Article]
- Banerjee T, Singh SK, Kishore N: Binding of naproxen and amitriptyline to bovine serum albumin: biophysical aspects. J Phys Chem B. 2006 Nov 30;110(47):24147-56. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Not Available
- Specific Function
- Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23511.38 Da
References
- Brinkschulte M, Breyer-Pfaff U: The contribution of alpha 1-acid glycoprotein, lipoproteins, and albumin to the plasma binding of perazine, amitriptyline, and nortriptyline in healthy man. Naunyn Schmiedebergs Arch Pharmacol. 1980 Oct;314(1):61-6. doi: 10.1007/bf00498432. [Article]
- Ferry DG, Caplan NB, Cubeddu LX: Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein. J Pharm Sci. 1986 Feb;75(2):146-9. doi: 10.1002/jps.2600750208. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- There are conflicting data in the literature regarding amitriptyline as a substrate for p-glycoprotein.
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Grauer MT, Uhr M: P-glycoprotein reduces the ability of amitriptyline metabolites to cross the blood brain barrier in mice after a 10-day administration of amitriptyline. J Psychopharmacol. 2004 Mar;18(1):66-74. doi: 10.1177/0269881104042831. [Article]
- O'Brien FE, Clarke G, Dinan TG, Cryan JF, Griffin BT: Human P-glycoprotein differentially affects antidepressant drug transport: relevance to blood-brain barrier permeability. Int J Neuropsychopharmacol. 2013 Nov;16(10):2259-72. doi: 10.1017/S1461145713000692. Epub 2013 Aug 9. [Article]
- Abaut AY, Chevanne F, Le Corre P: Oral bioavailability and intestinal secretion of amitriptyline: Role of P-glycoprotein? Int J Pharm. 2007 Feb 7;330(1-2):121-8. doi: 10.1016/j.ijpharm.2006.09.026. Epub 2006 Sep 23. [Article]
- Uhr M, Steckler T, Yassouridis A, Holsboer F: Penetration of amitriptyline, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to mdr1a P-glycoprotein gene disruption. Neuropsychopharmacology. 2000 Apr;22(4):380-7. doi: 10.1016/S0893-133X(99)00095-0. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55