Identification
- Summary
Duloxetine is a serotonin norepinephrine reuptake inhibitor used to treat generalized anxiety disorder, neuropathic pain, osteoarthritis, and stress incontinence.
- Brand Names
- Cymbalta, Drizalma, Irenka, Yentreve
- Generic Name
- Duloxetine
- DrugBank Accession Number
- DB00476
- Background
Duloxetine is a dual serotonin and norepinephrine reuptake inhibitor.Label It was originally discovered in 1993 and developed by Eli Lilly and Company as LY248686.15 Duloxetine first received approval from the FDA in August, 2004 as Cymbalta for the treatment of Major Depressive Disorder.20 It has since received approval for a variety of indications including the treatment of neuropathic pain, Generalized Anxiety disorder, osteoarthritis, and stress incontinence. Duloxetine continues to be investigated for the treatment of pain in cancer, surgery, and more.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Duloxetine (DB00476)
- Weight
- Average: 297.415
Monoisotopic: 297.118734925 - Chemical Formula
- C18H19NOS
- Synonyms
- (3S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propan-1-amine
- (S)-duloxetine
- Duloxetina
- Duloxetine
- External IDs
- LY 248686
- LY-248686
- LY248686
Pharmacology
- Indication
Indicated for:
1) Management of Major Depressive Disorder.Label
2) Management of Generalized Anxiety Disorder.Label
3) Management of diabetic peripheral neuropathy.Label
4) Management of fibromyalgia.Label
5) Management of chronic musculoskeletal pain.Label
6) Management of osteoarthritis of the knee in adults.17
7) Management of chronic lower back pain in adults.17
8) Management of stress urinary incontinence in adult women.18
Off-label uses include:
1) Management of chemotherapy-induced peripheral neuropathy.8
2) Management of stress urinary incontinence in adult men after prostatectomy until recovery is complete.19
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Chronic lower back pain •••••••••••• ••••• •••••••• ••••••• ••••••• ••••••• Management of Chronic musculoskeletal pain •••••••••••• ••••• •••••••• ••••••• ••••••• Management of Diabetic peripheral neuropathic pain (dpn) •••••••••••• ••••• •••••••• ••••••• ••••••• Management of Fibromyalgia (fm) •••••••••••• ••••• •••••••• ••••••• ••••••• Management of Generalized anxiety disorder •••••••••••• ••••••••••• •••••• ••••••••• •••••••• ••••••• ••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Duloxetine, through increasing serotonin and norepinephrine concentrations in Onuf's nucleus, enhances glutamatergic activation of the pudendal motor nerve which innervates the external urethral sphinter.9,10 This enhanced signaling allows for stronger contraction. Increased contraction of this sphincter increases the pressure needed to produce an incontinence episode in stress urinary incontinence. Duloxetine has been shown to improve Patient Global Impression of Improvement and Incontinence Quality of Life scores.11 It has also been shown to reduce the median incontinence episode frequency at doses of 40 and 80 mg.
Action at the dorsal horn of the spinal cord allows duloxetine to strengthen the the serotonergic and adrenergic pathways involved in descending inhibition of pain.10,12 This results in an increased threshold of activation necessary to transmit painful stimuli to the brain and effective relief of pain, particularly in neuropathic pain. Pain relief has been noted in a variety of painful conditions including diabetic peripheral neuropathy, fibromyalgia, and osteoarthritis using a range of pain assessment surveys.13
While duloxetine has been shown to be effective in both animal models of mood disorders and in clinical trials for the treatment of these disorders in humans, the broad scope of its pharmacodynamic effects on mood regulation in the brain has yet to be explained.14
Increased blood pressure is a common side effect with duloxetine due to vasoconstriction mediated by the intended increase in norepinephrine signaling.Label,16
- Mechanism of action
Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake.14 Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors.
Action on the external urinary sphincter is mediated via duloxetine's CNS effects. Increased serotonin and norepinephrine concentrations in Onuf's nucleus leads to increased activation of 5-HT2, 5-HT3, and α1 adrenergic receptors.9,10 5-HT2 and α1 are both Gq coupled and their activation increases the activity of the inositol trisphosphate/phospholipase C (IP3/PLC) pathway.16 This pathway leads to release of intracellular calcium stores, increasing intracellular calcium concentrations, and facilitating neuronal excitability. 5-HT3 functions as a ligand-gated sodium channel which allows sodium to flow into the neuron when activated. Increased flow of sodium into the neuron contributes to depolarization and activation of voltage gated channels involved in action potential generation. The combined action of these three receptors contributes to increased excitability of the pudendal motor nerve in response to glutamate.
Also related to duloxetine's action at the spinal cord is its modulation of pain. Increasing the concentration of serotonin and norepinephrine in the dorsal horn of the spinal cord increases descending inhibition of pain through activation of 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2, 5-HT3, α1-adrenergic, and α2-adrenergic receptors.12 5-HT2, 5-HT3, and α1-adrenergic mediate neuronal activation as described above. The activated neuron in this case is the GABAergic inhibitory interneuron which synapses onto the nociceptive projection neuron to inhibit the transmission of painful stimuli to the brain. The 5-HT1 and α2 receptors are Gi/Go coupled and their activation leads to increased potassium current through inward rectifier channels and decreased adenylyl cyclase/protein kinase A signaling which contributes to neuronal inhibition.12,16 These inhibitory receptors are present on the projection neuron itself as well as the dorsal root ganglion which precedes it and serves to directly suppress the transmission of painful stimuli.
The mechanisms involved in duloxetine's benefits in depression and anxiety have not been fully elucidated. Dysfunctional serotonin and norepinephrine signaling are thought to be involved and increases in the availability of these neurotransmitters at the synaptic cleft thought to mediate a therapeutic effect.10 It is postulated that the involvement of serotonin and norepinephrine in area responsible for emotional modulation such as the limbic system contributes to the effects in mood disorders specifically but this has yet to be confirmed.
Duloxetine's hypertensive effect is related to its intended pharmacological effect. Increased availability of norepinephrine leads to activation of adrenergic receptors on the vascular endothelium. Since the action of α1 receptors predominates, vasoconstriction results as the Gq coupled receptor mediates calcium release from the sarcoplasmic reticulum to facilitate smooth muscle contraction.16
Target Actions Organism ASodium-dependent serotonin transporter inhibitorHumans ASodium-dependent noradrenaline transporter inhibitorHumans USodium-dependent dopamine transporter inhibitorHumans - Absorption
Duloxetine is incompletely absorbed with a mean bioavailability of 50% although there is wide variability in the range of 30-80%.7 The population absorption constant (ka) is 0.168 h-1.The molecule is susceptible to hydrolysis in acidic environments necessitating the use of an enteric coating to protect it during transit through the stomach. This creates a 2 hour lag time from administration to the start of absorption. The Tmax is 6 hours including the lag time.Label Administering duloxetine with food 3 hour delay in Tmax along with an 10% decrease in AUC. Similarly, administering the dose at bedtime produces a 4 hour delay and 18% decrease in AUC with a 29% reduction in Cmax.7 These are attributed to delayed gastric emptying in both cases but are not expected to impact therapy to a clinically significant degree.
- Volume of distribution
Apparent Vd of 1620-1800 L.Label,7 Duloxetine crosses the blood-brain barrier and collects in the cerebral cortex at a higher concentration than the plasma.7
- Protein binding
Over 90% bound to plasma proteins, primarily albumin and α1 acid-glycoprotein.Label,7
- Metabolism
Duloxetine is extensively metabolized primarily by CYP1A2 and CYP2D6 with the former being the greater contributor.Label,7 It is hydroxylated at the 4, 5, or 6 positions on the naphthalene ring with the 4-hydroxy metabolite proceeding directly to a glucuronide conjugate while the 5 and 6-hydroxy metabolites proceed through a catechol and a 5-hydroxy, 6-methoxy intermediate before undergoing glucuronide or sulfate conjugation. CYP2C9 is known to be a minor contributor to the 5-hydroxy metabolite. Another uncharacterized metabolite is known to be excreted in the feces but comprises <5% of the total excreted drug. Many other metabolites exist but have not been identified due their low contribution to the overall profile of duloxetine and lack of clinical significance.
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- Route of elimination
About 70% of duloxetine is excreted in the urine mainly as conjugated metabolites.Label Another 20% is present in the feces as the parent drug, 4-hydroxy metabolite, and an uncharacterized metabolite.Label,7 Biliary secretion is thought to play a role due to timeline of fecal excretion exceeding the time expected of normal GI transit.7
- Half-life
- Clearance
There is a large degree of interindividual variation reported in the clearance of duloxetine with values ranging from 57-114 L/h.7 Steady state concentrations have still been shown to be dose proportional with a doubling of dose from 30 to 60 mg and from 60 to 120 mg producing 2.3 and 2.6 times the Css respectively.
- Adverse Effects
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Overdose
Fatalities have been reported with doses of 1000mg involving both mixed drugs as well as duloxetine alone.Label Signs and symptoms of overdose include: somnolence, coma, serotonin syndrome, seizure, syncope, hypo- or hypertension, tachycardia, and vomiting. No antidote exists and the drug is unlikely to be cleared by hemodialysis. Supportive care is recommended along with activated charcoal and gastric lavage to reduce absorption. If serotonin syndrome occurs specific treatment such as temperature control or cyproheptadine may be initiated.
Carcinogenicity & Mutagenicity
Increased incidence of hepatocellular carcinomas and adenomas were reported in female mice fed 140 mg/kg/day duloxetine for 2 years, equivalent to 6 times the maximum recommended human dose (MRHD).Label No effect was reported with doses of 50mg/kg/day (2 time MRHD) in females or 100 mg/kg/day in males (4 times MRHD). Similar investigation in rats produced no carcinogenicity at doses of 27 mg/kg/day (2 times MRHD)in females and 36 mg/kg/day in males (4 times MRHD).
No mutagenicity, clastogenicity, induction of sister chromatid exchange, or genotoxicity has been observed in toxicology investigations.
Reproductive Toxicity
Neither male or female rats displayed adverse reproductive effects at doses up to 45 mg/kg/day (4 times MRHD).Label
Lactation
An estimated 25% of plasma duloxetine appears in breast milk with the estimated daily infant dose being 0.14% of the maternal dose.Label Breast milk concentrations have been observed to peak 3 hours after administration.
- 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*3 Not Available C allele Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*4 Not Available C allele Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*5 Not Available Whole-gene deletion Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*6 Not Available 1707delT Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*7 Not Available 2935A>C Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*8 Not Available 1758G>T Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*11 Not Available 883G>C Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*12 Not Available 124G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*13 Not Available CYP2D7/2D6 hybrid gene structure Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*14A Not Available 1758G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*15 Not Available 137insT, 137_138insT Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*19 Not Available 2539_2542delAACT Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*20 Not Available 1973_1974insG Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*21 Not Available 2573insC Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*31 Not Available -1770G>A / -1584C>G … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*36 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*38 Not Available 2587_2590delGACT Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*40 Not Available 1863_1864ins(TTT CGC CCC)2 Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*42 Not Available 3259_3260insGT Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*44 Not Available 2950G>C Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*47 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*51 Not Available -1584C>G / -1235A>G … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*56 Not Available 3201C>T Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*57 Not Available 100C>T / 310G>T … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*62 Not Available 4044C>T Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*68A Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer. 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. Details Cytochrome P450 2D6 CYP2D6*69 Not Available 2988G>A / -1426C>T … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*92 Not Available 1995delC Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*100 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*101 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 1A2 CYP1A2*6 Not Available 5090C>T Effect Inferred Poor drug metabolizer. 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 adverse effects can be increased when 1,2-Benzodiazepine is combined with Duloxetine. Abacavir Duloxetine may decrease the excretion rate of Abacavir which could result in a higher serum level. Abaloparatide The risk or severity of orthostatic hypotension and syncope can be increased when Abaloparatide is combined with Duloxetine. Abatacept The metabolism of Duloxetine can be increased when combined with Abatacept. Abciximab The risk or severity of hemorrhage can be increased when Duloxetine is combined with Abciximab. - Food Interactions
- Avoid excessive or chronic alcohol consumption. Alcohol increases the risk of liver toxicity.
- Take with or without food. Do not sprinkle the contents of the capsules on food/liquids.
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 Duloxetine hydrochloride 9044SC542W 136434-34-9 BFFSMCNJSOPUAY-LMOVPXPDSA-N - Product Images
- International/Other Brands
- Dulane / Duzela
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ariclaim Capsule, delayed release 60 mg Oral Eli Lilly Nederland B.V. 2016-09-08 2018-08-07 EU 
Ariclaim Capsule, delayed release 30 mg Oral Eli Lilly Nederland B.V. 2016-09-08 2018-08-07 EU Ariclaim Capsule, delayed release 30 mg Oral Eli Lilly Nederland B.V. 2016-09-08 2018-08-07 EU Ariclaim Capsule, delayed release 60 mg Oral Eli Lilly Nederland B.V. 2016-09-08 2018-08-07 EU Ariclaim Capsule, delayed release 30 mg Oral Eli Lilly Nederland B.V. 2016-09-08 2018-08-07 EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Accel-duloxetine Capsule, delayed release 60 mg Oral Accel Pharma Inc 2022-04-04 Not applicable Canada 
Accel-duloxetine Capsule, delayed release 30 mg Oral Accel Pharma Inc 2022-04-04 Not applicable Canada Ag-duloxetine Capsule, delayed release 30 mg Oral Angita Pharma Inc. 2018-07-19 Not applicable Canada Ag-duloxetine Capsule, delayed release 60 mg Oral Angita Pharma Inc. 2018-07-19 Not applicable Canada Apo-duloxetine Capsule, delayed release 60 mg Oral Apotex Corporation 2016-05-03 Not applicable Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image DermacinRx DPN Pak Duloxetine hydrochloride (60 mg/1) + Lidocaine hydrochloride anhydrous (50 mg/1mL) + Menthol (30 mg/1mL) Kit Oral; Topical PureTek Corporation 2016-05-26 2017-08-17 US 
- Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Duloxicaine Duloxetine hydrochloride (30 mg/1) + Lidocaine hydrochloride (4 g/100g) Capsule, delayed release; Cream; Kit Oral; Topical V2 Pharma, LLC 2023-01-23 Not applicable US
Categories
- ATC Codes
- N06AX21 — Duloxetine
- Drug Categories
- Agents producing tachycardia
- Analgesics
- Antidepressive Agents
- Antidepressive Agents Indicated for Depression
- Central Nervous System Agents
- Central Nervous System Depressants
- Combined Inhibitors of Serotonin/Norepinephrine Reuptake
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (moderate)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Hypoglycemia-Associated Agents
- Membrane Transport Modulators
- Nervous System
- Neurotransmitter Uptake Inhibitors
- Norepinephrine Uptake Inhibitors
- P-glycoprotein inhibitors
- Peripheral Nervous System Agents
- Psychoanaleptics
- Psychotropic Drugs
- Selective Serotonin Reuptake Inhibitors
- Sensory System Agents
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin Agents
- Serotonin and Noradrenaline Reuptake Inhibitors
- Serotonin Modulators
- Sulfur Compounds
- Thiophenes
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as naphthalenes. These are compounds containing a naphthalene moiety, which consists of two fused benzene rings.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Naphthalenes
- Sub Class
- Not Available
- Direct Parent
- Naphthalenes
- Alternative Parents
- Aralkylamines / Alkyl aryl ethers / Thiophenes / Heteroaromatic compounds / Dialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Alkyl aryl ether / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Ether / Heteroaromatic compound / Hydrocarbon derivative / Naphthalene / Organic nitrogen compound / Organic oxygen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- duloxetine (CHEBI:36795)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- O5TNM5N07U
- CAS number
- 116539-59-4
- InChI Key
- ZEUITGRIYCTCEM-KRWDZBQOSA-N
- InChI
- InChI=1S/C18H19NOS/c1-19-12-11-17(18-10-5-13-21-18)20-16-9-4-7-14-6-2-3-8-15(14)16/h2-10,13,17,19H,11-12H2,1H3/t17-/m0/s1
- IUPAC Name
- methyl[(3S)-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propyl]amine
- SMILES
- CNCC[C@H](OC1=CC=CC2=CC=CC=C12)C1=CC=CS1
References
- Synthesis Reference
Richard A. Berglund, "Intermediate useful for the asymmetric synthesis of duloxetine." U.S. Patent US5491243, issued June, 1991.
US5491243- General References
- Turcotte JE, Debonnel G, de Montigny C, Hebert C, Blier P: Assessment of the serotonin and norepinephrine reuptake blocking properties of duloxetine in healthy subjects. Neuropsychopharmacology. 2001 May;24(5):511-21. [Article]
- Anttila S, Leinonen E: Duloxetine Eli Lilly. Curr Opin Investig Drugs. 2002 Aug;3(8):1217-21. [Article]
- Karpa KD, Cavanaugh JE, Lakoski JM: Duloxetine pharmacology: profile of a dual monoamine modulator. CNS Drug Rev. 2002 Winter;8(4):361-76. [Article]
- van Groeningen CJ, Peters GJ, Pinedo HM: Lack of effectiveness of combined 5-fluorouracil and leucovorin in patients with 5-fluorouracil-resistant advanced colorectal cancer. Eur J Cancer Clin Oncol. 1989 Jan;25(1):45-9. [Article]
- Jost W, Marsalek P: Duloxetine: mechanism of action at the lower urinary tract and Onuf's nucleus. Clin Auton Res. 2004 Aug;14(4):220-7. [Article]
- Carter NJ, McCormack PL: Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006. [Article]
- Knadler MP, Lobo E, Chappell J, Bergstrom R: Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2011 May;50(5):281-94. doi: 10.2165/11539240-000000000-00000. [Article]
- Hershman DL, Lacchetti C, Loprinzi CL: Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline Summary. J Oncol Pract. 2014 Nov;10(6):e421-e424. doi: 10.1200/JOP.2014.001776. [Article]
- de Groat WC, Yoshimura N: Pharmacology of the lower urinary tract. Annu Rev Pharmacol Toxicol. 2001;41:691-721. doi: 10.1146/annurev.pharmtox.41.1.691. [Article]
- Thor KB, Kirby M, Viktrup L: Serotonin and noradrenaline involvement in urinary incontinence, depression and pain: scientific basis for overlapping clinical efficacy from a single drug, duloxetine. Int J Clin Pract. 2007 Aug;61(8):1349-55. doi: 10.1111/j.1742-1241.2007.01433.x. Epub 2007 Jun 30. [Article]
- Basu M, Duckett J: The treatment of urinary incontinence with Duloxetine. J Obstet Gynaecol. 2008 Feb;28(2):166-9. doi: 10.1080/01443610801912931. [Article]
- Millan MJ: Descending control of pain. Prog Neurobiol. 2002 Apr;66(6):355-474. [Article]
- Bellingham GA, Peng PW: Duloxetine: a review of its pharmacology and use in chronic pain management. Reg Anesth Pain Med. 2010 May-Jun;35(3):294-303. doi: 10.1097/AAP.0b013e3181df2645. [Article]
- Gupta S, Nihalani N, Masand P: Duloxetine: review of its pharmacology, and therapeutic use in depression and other psychiatric disorders. Ann Clin Psychiatry. 2007 Apr-Jun;19(2):125-32. doi: 10.1080/10401230701333319. [Article]
- Wong DT, Bymaster FP, Mayle DA, Reid LR, Krushinski JH, Robertson DW: LY248686, a new inhibitor of serotonin and norepinephrine uptake. Neuropsychopharmacology. 1993 Jan;8(1):23-33. doi: 10.1038/npp.1993.4. [Article]
- David R. Sibley; Lisa A. Hazelwood; Susan G. Amara (2018). 13. In Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education. [ISBN:978-1-25-958473-2]
- Cymbalta Health Canada Monograph [Link]
- Yentreve EMA SmPC [Link]
- EAU Stress Urinary Incontinence Guidelines [Link]
- Original FDA Label Cymbalta [Link]
- FDA Approved Products: Cymbalta (duloxetine) oral capsules [Link]
- FDA Approved Drug Products: CYMBALTA (duloxetine) delayed-release capsules [Link]
- FDA Approved Drug Products: CYMBALTA (duloxetine) delayed-release capsules (August 2023) [Link]
- External Links
- Human Metabolome Database
- HMDB0014619
- PubChem Compound
- 60835
- PubChem Substance
- 46507937
- ChemSpider
- 54822
- BindingDB
- 84745
- 72625
- ChEBI
- 36795
- ChEMBL
- CHEMBL1175
- ZINC
- ZINC000001536779
- Therapeutic Targets Database
- DAP000494
- PharmGKB
- PA10066
- Guide to Pharmacology
- GtP Drug Page
- PDBe Ligand
- 29E
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Duloxetine
- PDB Entries
- 4mm6 / 4mmd / 6m38
- FDA label
- Download (104 KB)
- MSDS
- Download (76.3 KB)
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 Basic Science None (i.e. Healthy Volunteers) 1 4 Active Not Recruiting Treatment Chronic Lower Back Pain (CLBP) 1 4 Completed Basic Science Coronavirus Disease 2019 (COVID‑19) / Myocarditis Allergic / Renal Dialysis / Severe Acute Respiratory Syndrome-related Coronavirus / Vaccines / Viral Infections 1 4 Completed Basic Science Healthy Subjects (HS) 1 4 Completed Basic Science Healthy Subjects (HS) / Major Depressive Disorder (MDD) 1
Pharmacoeconomics
- Manufacturers
- Eli lilly and co
- Packagers
- Bryant Ranch Prepack
- Cardinal Health
- Diversified Healthcare Services Inc.
- Eli Lilly & Co.
- Innoviant Pharmacy Inc.
- Kaiser Foundation Hospital
- Lake Erie Medical and Surgical Supply
- Lilly Del Caribe Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Nucare Pharmaceuticals Inc.
- Palmetto Pharmaceuticals Inc.
- PD-Rx Pharmaceuticals Inc.
- Pharmacy Service Center
- Physicians Total Care Inc.
- Rebel Distributors Corp.
- Remedy Repack
- Resource Optimization and Innovation LLC
- Southwood Pharmaceuticals
- Stat Rx Usa
- Vangard Labs Inc.
- Dosage Forms
Form Route Strength Capsule Oral 67.300 mg Tablet, delayed release Oral 3000000 mg Capsule Oral 30.000 mg Capsule Oral Capsule Oral 33.7 MG Capsule Oral 67.3 MG Capsule, delayed release Oral 20 mg/1 Capsule, delayed release Oral 30 mg/1 Capsule, delayed release Oral 60 mg/1 Capsule, delayed release Oral 30 mg Capsule, delayed release Oral 60 mg Capsule Oral 30.0 mg Capsule Oral 60.0 mg Kit Oral; Topical Capsule Oral 33.680 mg Capsule Oral 30.000 mg Capsule, delayed release Oral 90 MG Capsule, delayed release Oral 20 MG Capsule, delayed release Oral 40 MG Capsule, delayed release Oral Capsule, delayed release Oral 45 MG Capsule, delayed release Oral 120 MG Capsule Oral 30 MG Capsule Oral 60 MG Capsule, delayed release pellets Oral 20 mg/1 Capsule, delayed release pellets Oral 30 mg/1 Capsule, delayed release pellets Oral 60 mg/1 Capsule, delayed release pellets Oral 40 mg/1 Capsule, delayed release; cream; kit Oral; Topical Capsule, extended release Capsule Oral 30.00 mg Tablet, delayed release Oral 30 MG Tablet, delayed release Oral 60 MG Capsule, coated Oral 60 mg Capsule Oral 60.000 mg Capsule, coated Oral 30 mg Capsule, delayed release Oral 40 mg/1 Tablet Oral 33.680 mg Capsule Oral 33.690 mg Capsule Oral 20 mg Capsule Oral 40 mg Capsule, coated Oral 6000000 mg Capsule, delayed release Oral 33.66 mg Capsule, delayed release Oral 67.32 mg Capsule Oral 336.780 mg Capsule Oral 33.680 mg - Prices
Unit description Cost Unit Cymbalta 30 mg Enteric Coated Capsule 5.38USD capsule Cymbalta 60 mg Enteric Coated Capsule 5.38USD capsule Cymbalta 30 mg capsule 5.18USD capsule Cymbalta 60 mg capsule 5.18USD capsule Cymbalta 20 mg Enteric Coated Capsule 4.64USD capsule Cymbalta 20 mg capsule 4.62USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5023269 No 1991-06-11 2013-06-11 US CA2344057 No 2008-11-18 2019-09-10 Canada CA2153856 No 2005-05-10 2015-07-13 Canada US6596756 Yes 2003-07-22 2020-03-10 US US9839626 No 2017-12-12 2037-04-13 US US10413525 No 2019-09-17 2037-04-13 US US10959982 No 2021-03-30 2037-04-13 US US11202772 No 2021-12-21 2037-04-13 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 4 Not Available - Predicted Properties
Property Value Source Water Solubility 0.00296 mg/mL ALOGPS logP 4.72 ALOGPS logP 4.2 Chemaxon logS -5 ALOGPS pKa (Strongest Basic) 9.7 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 21.26 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 87.73 m3·mol-1 Chemaxon Polarizability 33.15 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 Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9804 Caco-2 permeable + 0.6358 P-glycoprotein substrate Substrate 0.7078 P-glycoprotein inhibitor I Inhibitor 0.5987 P-glycoprotein inhibitor II Non-inhibitor 0.5519 Renal organic cation transporter Inhibitor 0.6525 CYP450 2C9 substrate Non-substrate 0.5964 CYP450 2D6 substrate Substrate 0.6482 CYP450 3A4 substrate Substrate 0.5799 CYP450 1A2 substrate Inhibitor 0.839 CYP450 2C9 inhibitor Non-inhibitor 0.7721 CYP450 2D6 inhibitor Inhibitor 0.6977 CYP450 2C19 inhibitor Non-inhibitor 0.572 CYP450 3A4 inhibitor Inhibitor 0.5108 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6689 Ames test Non AMES toxic 0.5422 Carcinogenicity Non-carcinogens 0.9293 Biodegradation Not ready biodegradable 0.935 Rat acute toxicity 2.5700 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.5926 hERG inhibition (predictor II) Inhibitor 0.6386
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 177.174442 predictedDarkChem Lite v0.1.0 [M-H]- 176.888042 predictedDarkChem Lite v0.1.0 [M-H]- 162.97807 predictedDeepCCS 1.0 (2019) [M+H]+ 177.975642 predictedDarkChem Lite v0.1.0 [M+H]+ 177.714342 predictedDarkChem Lite v0.1.0 [M+H]+ 165.33607 predictedDeepCCS 1.0 (2019) [M+Na]+ 177.640842 predictedDarkChem Lite v0.1.0 [M+Na]+ 177.502342 predictedDarkChem Lite v0.1.0 [M+Na]+ 171.58986 predictedDeepCCS 1.0 (2019)
Targets
- 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
- Chen F, Larsen MB, Sanchez C, Wiborg O: The S-enantiomer of R,S-citalopram, increases inhibitor binding to the human serotonin transporter by an allosteric mechanism. Comparison with other serotonin transporter inhibitors. Eur Neuropsychopharmacol. 2005 Mar;15(2):193-8. [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]
- Gould GG, Javors MA, Frazer A: Effect of chronic administration of duloxetine on serotonin and norepinephrine transporter binding sites in rat brain. Biol Psychiatry. 2007 Jan 15;61(2):210-5. Epub 2006 May 2. [Article]
- Mirza NR, Nielsen EO, Troelsen KB: Serotonin transporter density and anxiolytic-like effects of antidepressants in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2007 May 9;31(4):858-66. Epub 2007 Jan 30. [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]
- Beique JC, Lavoie N, de Montigny C, Debonnel G: Affinities of venlafaxine and various reuptake inhibitors for the serotonin and norepinephrine transporters. Eur J Pharmacol. 1998 May 15;349(1):129-32. [Article]
- Karpa KD, Cavanaugh JE, Lakoski JM: Duloxetine pharmacology: profile of a dual monoamine modulator. CNS Drug Rev. 2002 Winter;8(4):361-76. [Article]
- van Groeningen CJ, Peters GJ, Pinedo HM: Lack of effectiveness of combined 5-fluorouracil and leucovorin in patients with 5-fluorouracil-resistant advanced colorectal cancer. Eur J Cancer Clin Oncol. 1989 Jan;25(1):45-9. [Article]
- Jost W, Marsalek P: Duloxetine: mechanism of action at the lower urinary tract and Onuf's nucleus. Clin Auton Res. 2004 Aug;14(4):220-7. [Article]
- Trivedi MH, Desaiah D, Ossanna MJ, Pritchett YL, Brannan SK, Detke MJ: Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine. Int Clin Psychopharmacol. 2008 May;23(3):161-9. doi: 10.1097/YIC.0b013e3282f41d7e. [Article]
- Bymaster FP, Lee TC, Knadler MP, Detke MJ, Iyengar S: The dual transporter inhibitor duloxetine: a review of its preclinical pharmacology, pharmacokinetic profile, and clinical results in depression. Curr Pharm Des. 2005;11(12):1475-93. [Article]
- Khullar V, Cardozo L, Dmochowski R: Mixed incontinence: current evidence and future perspectives. Neurourol Urodyn. 2010 Apr;29(4):618-22. doi: 10.1002/nau.20907. [Article]
- Carter NJ, McCormack PL: Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006. [Article]
- Hunziker ME, Suehs BT, Bettinger TL, Crismon ML: Duloxetine hydrochloride: a new dual-acting medication for the treatment of major depressive disorder. Clin Ther. 2005 Aug;27(8):1126-43. [Article]
- 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
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Gould GG, Javors MA, Frazer A: Effect of chronic administration of duloxetine on serotonin and norepinephrine transporter binding sites in rat brain. Biol Psychiatry. 2007 Jan 15;61(2):210-5. Epub 2006 May 2. [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]
- Beique JC, Lavoie N, de Montigny C, Debonnel G: Affinities of venlafaxine and various reuptake inhibitors for the serotonin and norepinephrine transporters. Eur J Pharmacol. 1998 May 15;349(1):129-32. [Article]
- Vincent S, Bieck PR, Garland EM, Loghin C, Bymaster FP, Black BK, Gonzales C, Potter WZ, Robertson D: Clinical assessment of norepinephrine transporter blockade through biochemical and pharmacological profiles. Circulation. 2004 Jun 29;109(25):3202-7. Epub 2004 Jun 7. [Article]
- Schou M, Halldin C, Pike VW, Mozley PD, Dobson D, Innis RB, Farde L, Hall H: Post-mortem human brain autoradiography of the norepinephrine transporter using (S,S)-[18F]FMeNER-D2. Eur Neuropsychopharmacol. 2005 Oct;15(5):517-20. Epub 2005 Apr 7. [Article]
- Mirza NR, Nielsen EO, Troelsen KB: Serotonin transporter density and anxiolytic-like effects of antidepressants in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2007 May 9;31(4):858-66. Epub 2007 Jan 30. [Article]
- Karpa KD, Cavanaugh JE, Lakoski JM: Duloxetine pharmacology: profile of a dual monoamine modulator. CNS Drug Rev. 2002 Winter;8(4):361-76. [Article]
- van Groeningen CJ, Peters GJ, Pinedo HM: Lack of effectiveness of combined 5-fluorouracil and leucovorin in patients with 5-fluorouracil-resistant advanced colorectal cancer. Eur J Cancer Clin Oncol. 1989 Jan;25(1):45-9. [Article]
- Jost W, Marsalek P: Duloxetine: mechanism of action at the lower urinary tract and Onuf's nucleus. Clin Auton Res. 2004 Aug;14(4):220-7. [Article]
- Trivedi MH, Desaiah D, Ossanna MJ, Pritchett YL, Brannan SK, Detke MJ: Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine. Int Clin Psychopharmacol. 2008 May;23(3):161-9. doi: 10.1097/YIC.0b013e3282f41d7e. [Article]
- Bymaster FP, Lee TC, Knadler MP, Detke MJ, Iyengar S: The dual transporter inhibitor duloxetine: a review of its preclinical pharmacology, pharmacokinetic profile, and clinical results in depression. Curr Pharm Des. 2005;11(12):1475-93. [Article]
- Khullar V, Cardozo L, Dmochowski R: Mixed incontinence: current evidence and future perspectives. Neurourol Urodyn. 2010 Apr;29(4):618-22. doi: 10.1002/nau.20907. [Article]
- Carter NJ, McCormack PL: Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006. [Article]
- Hunziker ME, Suehs BT, Bettinger TL, Crismon ML: Duloxetine hydrochloride: a new dual-acting medication for the treatment of major depressive disorder. Clin Ther. 2005 Aug;27(8):1126-43. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Monoamine transmembrane transporter activity
- Specific Function
- Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name
- SLC6A3
- Uniprot ID
- Q01959
- Uniprot Name
- Sodium-dependent dopamine transporter
- Molecular Weight
- 68494.255 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Carter NJ, McCormack PL: Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006. [Article]
- Pereira P, Gianesini J, da Silva Barbosa C, Cassol GF, Von Borowski RG, Kahl VF, Cappelari SE, Picada JN: Neurobehavioral and genotoxic parameters of duloxetine in mice using the inhibitory avoidance task and comet assay as experimental models. Pharmacol Res. 2009 Jan;59(1):57-61. doi: 10.1016/j.phrs.2008.09.014. Epub 2008 Oct 5. [Article]
- Hunziker ME, Suehs BT, Bettinger TL, Crismon ML: Duloxetine hydrochloride: a new dual-acting medication for the treatment of major depressive disorder. Clin Ther. 2005 Aug;27(8):1126-43. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- Knadler MP, Lobo E, Chappell J, Bergstrom R: Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2011 May;50(5):281-94. doi: 10.2165/11539240-000000000-00000. [Article]
- Preskorn SH, Nichols AI, Paul J, Patroneva AL, Helzner EC, Guico-Pabia CJ: Effect of desvenlafaxine on the cytochrome P450 2D6 enzyme system. J Psychiatr Pract. 2008 Nov;14(6):368-78. doi: 10.1097/01.pra.0000341891.43501.6b. [Article]
- Authors unspecified: Duloxetine: new indication. Depression and diabetic neuropathy: too many adverse effects. Prescrire Int. 2006 Oct;15(85):168-72. [Article]
- Carter NJ, McCormack PL: Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006. [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
- Knadler MP, Lobo E, Chappell J, Bergstrom R: Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2011 May;50(5):281-94. doi: 10.2165/11539240-000000000-00000. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Duloxetine causes time-dependent inhibition of CYP1A2, CYP2B6, CYP2C19 and CYP3A4/5.
- 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
- Chan CY, New LS, Ho HK, Chan EC: Reversible time-dependent inhibition of cytochrome P450 enzymes by duloxetine and inertness of its thiophene ring towards bioactivation. Toxicol Lett. 2011 Oct 30;206(3):314-24. doi: 10.1016/j.toxlet.2011.07.019. Epub 2011 Aug 5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Duloxetine causes time-dependent inhibition of CYP1A2, CYP2B6, CYP2C19 and CYP3A4/5.
- 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
- Knadler MP, Lobo E, Chappell J, Bergstrom R: Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2011 May;50(5):281-94. doi: 10.2165/11539240-000000000-00000. [Article]
- Lobo ED, Bergstrom RF, Reddy S, Quinlan T, Chappell J, Hong Q, Ring B, Knadler MP: In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine. Clin Pharmacokinet. 2008;47(3):191-202. [Article]
- Authors unspecified: Duloxetine: new indication. Depression and diabetic neuropathy: too many adverse effects. Prescrire Int. 2006 Oct;15(85):168-72. [Article]
- Carter NJ, McCormack PL: Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006. [Article]
- Chan CY, New LS, Ho HK, Chan EC: Reversible time-dependent inhibition of cytochrome P450 enzymes by duloxetine and inertness of its thiophene ring towards bioactivation. Toxicol Lett. 2011 Oct 30;206(3):314-24. doi: 10.1016/j.toxlet.2011.07.019. Epub 2011 Aug 5. [Article]
- Duloxetine FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Duloxetine causes time-dependent inhibition of CYP1A2, CYP2B6, CYP2C19 and CYP3A4/5.
- 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
- Chan CY, New LS, Ho HK, Chan EC: Reversible time-dependent inhibition of cytochrome P450 enzymes by duloxetine and inertness of its thiophene ring towards bioactivation. Toxicol Lett. 2011 Oct 30;206(3):314-24. doi: 10.1016/j.toxlet.2011.07.019. Epub 2011 Aug 5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Duloxetine causes time-dependent inhibition of CYP1A2, CYP2B6, CYP2C19 and CYP3A4/5.
- 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
- Chan CY, New LS, Ho HK, Chan EC: Reversible time-dependent inhibition of cytochrome P450 enzymes by duloxetine and inertness of its thiophene ring towards bioactivation. Toxicol Lett. 2011 Oct 30;206(3):314-24. doi: 10.1016/j.toxlet.2011.07.019. Epub 2011 Aug 5. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Ligand
- 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
- Knadler MP, Lobo E, Chappell J, Bergstrom R: Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2011 May;50(5):281-94. doi: 10.2165/11539240-000000000-00000. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Ligand
- 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...
Components:
References
- Knadler MP, Lobo E, Chappell J, Bergstrom R: Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2011 May;50(5):281-94. doi: 10.2165/11539240-000000000-00000. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- Ruike Z, Junhua C, Wenxing P: In vitro and in vivo evaluation of the effects of duloxetine on P-gp function. Hum Psychopharmacol. 2010 Nov;25(7-8):553-9. doi: 10.1002/hup.1152. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55