Identification
- Generic Name
- Lorpiprazole
- DrugBank Accession Number
- DB09195
- Background
Lorpiprazole is a serotonin antagonist and reuptake inhibitor used for the treatment of major depressive disorder.1 It is a piperazinyl-triazole derivative.3
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Lorpiprazole (DB09195)
- Weight
- Average: 405.469
Monoisotopic: 405.214030346 - Chemical Formula
- C21H26F3N5
- Synonyms
- Lorpiprazole
Pharmacology
- Indication
In 2016, lorpiprazole was classified in the "Chemical structure-related drug-like criteria of global approved drugs" as an antipsychotic and anxiolytic.6 An antipsychotic is a medication used to treat a state of delusion, hallucination, paranoia or disordered thought. On the other hand, an anxiolytic is a medication used for the treatment of severe, chronic or debilitating anxiety. The anxiety state can be defined as an unpleasant state of tension, apprehension or uneasiness.4
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- 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
Drugs like lorpiprazole that fit in the category of serotonin antagonists and reuptake inhibitors present a wide variety of effects when administered. They inhibit serotonin receptors like 5-HT2A as well as prevent the reuptake of serotonin, norepinephrine and dopamine. Additionally, they antagonize some adrenergic receptors. This diverse functional profile allows lorpiprazole to have a large therapeutic spectrum from symptom control as an adjuvant of other drugs to control of depressive syndromes as a monotherapy.2
- Mechanism of action
Lorpiprazole is a serotonin antagonist and reuptake inhibitor thus, its activity is performed by antagonizing the 5-HT2A and the 5-HT2C serotoninergic receptors as well as the alpha1 and alpha2 adrenergic receptors, H1 histaminergic receptors and at high doses, inhibiting the SERT serotonin transporter.2
Target Actions Organism A5-hydroxytryptamine receptor 2A antagonistHumans A5-hydroxytryptamine receptor 2C antagonistHumans AAlpha-1 adrenergic receptors antagonistHumans AAlpha-2 adrenergic receptors antagonistHumans AHistamine H1 receptor antagonistHumans ASodium-dependent serotonin transporter antagonistHumans - Absorption
After oral administration, the serotonin antagonist and reuptake inhibitors are rapidly absorbed in the gastrointestinal tract. This absorption can be slow down depending on the type of diet. The maximum plasma concentration of this kind of drugs occurs approximately 1 hour after administration.5
- Volume of distribution
The serotonin antagonists and reuptake inhibitors as lorpiprazole are quickly distributed through the blood-brain-barrier getting concentrated in the brain to even higher levels than the ones found in plasma.5
- Protein binding
The plasma protein binding of serotonin antagonists and reuptake inhibitors like lorpiprazole is expected to be very high and correspond to even 89-99% of the administered dose.5
- Metabolism
Serotonin antagonists and reuptake inhibitors like lorpiprazole are metabolized in the liver by the CYP450 isoenzymes, mainly CYP2D6 and CYP3A4.2
- Route of elimination
The elimination of drugs that fit in the category of serotonin antagonists and reuptake inhibitors like lorpiprazole is expected to have a biphasic profile in which most of the metabolized drug should be disposed of by the urine.5
- Half-life
The estimated half-life for drugs like lorpiprazole, a serotonin antagonist and reuptake inhibitor, is in the range of 11-23 hours.5
- Clearance
Not Available
- Adverse Effects
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The serotonin antagonists and reuptake inhibitors' side effects are minor with rare reports of cardiotoxicity. They have been reported to cause an unbalance between the sympathetic and parasympathetic system. There are also reports regarding a potential hepatotoxic effect of this drugs.5
- 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);">
- Not Available
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 sedation can be increased when Lorpiprazole is combined with 1,2-Benzodiazepine. Abacavir Abacavir may decrease the excretion rate of Lorpiprazole which could result in a higher serum level. Abametapir The serum concentration of Lorpiprazole can be increased when it is combined with Abametapir. Abatacept The metabolism of Lorpiprazole can be increased when combined with Abatacept. Abiraterone The metabolism of Lorpiprazole can be decreased when combined with Abiraterone. - Food Interactions
- Not Available
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.- International/Other Brands
- Normarex
Categories
- Drug Categories
- Antidepressive Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin 5-HT2C Receptor Antagonists
- Serotonin Agents
- Serotonin Modulators
- Serotonin Receptor Antagonists
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazinanes
- Sub Class
- Piperazines
- Direct Parent
- Phenylpiperazines
- Alternative Parents
- N-arylpiperazines / Trifluoromethylbenzenes / Dialkylarylamines / Aniline and substituted anilines / N-alkylpiperazines / Aralkylamines / Triazoles / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds show 4 more
- Substituents
- 1,2,4-triazole / Alkyl fluoride / Alkyl halide / Amine / Aniline or substituted anilines / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid show 16 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 0M14O7T47Q
- CAS number
- 108785-69-9
- InChI Key
- BNRMWKUVWLKDQJ-YJBOKZPZSA-N
- InChI
- InChI=1S/C21H26F3N5/c22-21(23,24)16-4-2-5-17(13-16)28-11-9-27(10-12-28)8-7-19-25-26-20-18-6-1-3-15(18)14-29(19)20/h2,4-5,13,15,18H,1,3,6-12,14H2/t15-,18-/m0/s1
- IUPAC Name
- (1S,8R)-5-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)-3,4,6-triazatricyclo[6.3.0.0²,⁶]undeca-2,4-diene
- SMILES
- [H][C@@]12CCC[C@]1([H])C1=NN=C(CCN3CCN(CC3)C3=CC=CC(=C3)C(F)(F)F)N1C2
References
- General References
- Fagiolini A, Comandini A, Catena Dell'Osso M, Kasper S: Rediscovering trazodone for the treatment of major depressive disorder. CNS Drugs. 2012 Dec;26(12):1033-49. doi: 10.1007/s40263-012-0010-5. [Article]
- Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]
- Elks J. and Ganellin C.R. (1990). The dictionary of drugs. Springer Science.
- Clark M., Harvey R., Finkel R., Rey J. and Whalen K. (2011). Pharmacology (5th ed.). Lippincott Williams & Wilkins.
- Szyndler J., Skorzewska A. and Plaznik A. (2003). Pharmacotherapy in psychiatry and neurology (3rd ed.). Institute of psychiatry and neurology.
- Molecules 2016 [Link]
- External Links
- PubChem Compound
- 20055414
- PubChem Substance
- 310265103
- ChemSpider
- 16736802
- ZINC
- ZINC000000537940
- Wikipedia
- Lorpiprazole
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
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 138 ºC Elks J. The Dictionary of Drugs. (1990) logP 3.02 DrugCentral logS -3.63 DrugCentral - Predicted Properties
Property Value Source Water Solubility 0.095 mg/mL ALOGPS logP 3.64 ALOGPS logP 3.22 Chemaxon logS -3.6 ALOGPS pKa (Strongest Basic) 7.57 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 37.19 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 108.4 m3·mol-1 Chemaxon Polarizability 42.08 Å3 Chemaxon Number of Rings 5 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
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0000900000-9bdd45743e069cefdb8c Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0udi-0000900000-e63d94b7416cf8b434a2 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0002900000-a030ebd81e5c0166a3da Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0udi-0002900000-71c2f40a050270f09b68 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-1049100000-477cf170ab2ae5c5343b Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0i00-0695300000-fb32a2a8f4dce1f7eb5e Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 193.79022 predictedDeepCCS 1.0 (2019) [M+H]+ 196.14822 predictedDeepCCS 1.0 (2019) [M+Na]+ 203.21112 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- 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
- Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- 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
- Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- 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...
Components:
| Name | UniProt ID |
|---|---|
| Alpha-1A adrenergic receptor | P35348 |
| Alpha-1B adrenergic receptor | P35368 |
| Alpha-1D adrenergic receptor | P25100 |
References
- Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- 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...
Components:
| Name | UniProt ID |
|---|---|
| Alpha-2A adrenergic receptor | P08913 |
| Alpha-2B adrenergic receptor | P18089 |
| Alpha-2C adrenergic receptor | P18825 |
References
- Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- 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
- Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- 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
- Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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
Drug created at October 16, 2015 21:28 / Updated at February 21, 2021 18:52