Identification
- Generic Name
- Pirlindole
- DrugBank Accession Number
- DB09244
- Background
This drug is classified as a reversible inhibitor of monoamine oxidase A enzyme (also known as a RIMA drug). It was developed and is currently used as an antidepressant in Russia. Its chemical structure is similar to metralindole, and it also shares pharmacological properties with this drug.
Pirlindole is a selective, reversible inhibitor of monoamine oxidase (MAO) subtype A (MAO-A) that is approved in several European and non-European countries for the treatment of major depression. The antidepressant efficacy and safety of pirlindole have been demonstrated in numerous studies and, supported by many years of clinical experience in the treatment of depression. Pirlindole's efficacy and safety have also been shown in the treatment of fibromyalgia.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Pirlindole (DB09244)
- Weight
- Average: 226.323
Monoisotopic: 226.146998588 - Chemical Formula
- C15H18N2
- Synonyms
- 2,3,3a,4,5,6-Hexahydro-8-methyl-1H-pyrazino(3,2,1-jk)carbazole
- Pirlindol
- Pirlindole
- Pirlindolum
Pharmacology
- Indication
For the treatment of major depression.
It is being studied in the treatment of fibromyalgia pain syndrome. One study determined that the effect of pirlindole on sensorimotor performance while driving a motor vehicle shows many similarities to that of placebo. The drug appears to stimulate the central nervous system, rather than exhibit a sedative effect, like many antidepressants. Because of its selective, reversible inhibition of monoamine oxidase (MAO-A) and short half-life, unpleasant "cheese effects" are avoided. This refers to the effects of consuming tyramine-rich foods, such as cheese while medicated with monoamine oxidase inhibitors, leading to severe headaches and hypertension 6. of The available evidence supports pirlindole as a safe and effective treatment option for the management of depression and fibromyalgia syndrome 5.
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
Pirlindole regulates that metabolism of norepinephrine and catecholamines, leading to relief of depressive symptoms. The prevention of breakdown of these neuromodulators is thought to elevate mood.
- Mechanism of action
This drug is a selective and reversible inhibitor of monoamine oxidase A (also known as MAO-A). Its main mechanism of action is selective and reversible inhibition of monoamine oxidase A. Its secondary mechanism of action is the inhibition effect of noradrenaline and 5-hydroxytryptamine reuptake 2.
Target Actions Organism UAmine oxidase [flavin-containing] A antagonistHumans U5-hydroxytryptamine receptor 1A antagonistHumans UAlpha-2A adrenergic receptor antagonistHumans - Absorption
Well absorbed with a bioavailability of 90% 3.
- Volume of distribution
Not Available
- Protein binding
97% binding to plasma proteins
- Metabolism
The drug is metabolized significantly through the hepatic system. From studies in dogs and rats, pirlindole has a bioavailability of between 20 and 30% due to the hepatic first-pass effect on this medication 2. The rat eliminates mainly unconjugated drug while the dog eliminates mostly conjugated drug 2.
- Route of elimination
Mainly renal, with 0.4-0.5% being excreted in the urine as unchanged drug in healthy males 3. Renal excretion was the main route of elimination of the metabolites in man 3.
- Half-life
0.7±0.3 in one study of healthy volunteers 3
- Clearance
High plasma clearance (450–1000 1/h) 3 in one study.
- Adverse Effects
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Short-acting selective and reversible monoamine oxidase A inhibitors, such as pirlindole, are commonly well-tolerated during an overdose. When taken alone, the clinical course is usually well-tolerated and benign.
Deaths from an overdose of this medication have more commonly observed during interactions with tyramine-rich foods tricyclic antidepressants (TCAs), or sympathomimetic drugs, and selective serotonin reuptake inhibitors (SSRIs). The clinical course of adverse effects from these conditions includes agitation, extreme tremor, followed by seizures and hyperthermia. Deaths occurred 3-16 hours after ingestion, after intractable seizure and/or hyperthermia and its sequelae, such as disseminated intravascular coagulation (DIC) and multi-organ failure 7.
- 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 CNS depression can be increased when Pirlindole is combined with 1,2-Benzodiazepine. Abacavir Abacavir may decrease the excretion rate of Pirlindole which could result in a higher serum level. Abaloparatide Pirlindole may increase the orthostatic hypotensive activities of Abaloparatide. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Pirlindole is combined with Abciximab. Acarbose Pirlindole may increase the hypoglycemic activities of Acarbose. - 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.- Product Ingredients
Ingredient UNII CAS InChI Key Pirlindole hydrochloride Q89W8I397C 16154-78-2 LIFOOCLGAAEVIF-UHFFFAOYSA-N Pirlindole lactate PRE19MC9Y9 292039-20-4 PXRNCRKTECAYRB-UHFFFAOYSA-N
Categories
- Drug Categories
- Agents that produce hypertension
- Agents that reduce seizure threshold
- Antidepressive Agents
- Central Nervous System Agents
- Central Nervous System Depressants
- Drugs that are Mainly Renally Excreted
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Indoles
- Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates
- Monoamine Oxidase Inhibitors
- Psychotropic Drugs
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin 5-HT1 Receptor Antagonists
- Serotonin 5-HT1A Receptor Antagonists
- Serotonin Agents
- Serotonin Receptor Antagonists
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as carbazoles. These are compounds containing a three ring system containing a pyrrole ring fused on either side to a benzene ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Carbazoles
- Direct Parent
- Carbazoles
- Alternative Parents
- 3-alkylindoles / Aralkylamines / Benzenoids / Pyrroles / Heteroaromatic compounds / Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- 3-alkylindole / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbazole / Heteroaromatic compound / Hydrocarbon derivative / Indole
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- V39YPH45FZ
- CAS number
- 60762-57-4
- InChI Key
- IWVRVEIKCBFZNF-UHFFFAOYSA-N
- InChI
- InChI=1S/C15H18N2/c1-10-5-6-14-12(9-10)11-3-2-4-13-15(11)17(14)8-7-16-13/h5-6,9,13,16H,2-4,7-8H2,1H3
- IUPAC Name
- 12-methyl-1,4-diazatetracyclo[7.6.1.0⁵,¹⁶.0¹⁰,¹⁵]hexadeca-9(16),10,12,14-tetraene
- SMILES
- CC1=CC=C2N3CCNC4CCCC(=C34)C2=C1
References
- Synthesis Reference
http://www.biomedsearch.com/nih/Pirlindole-in-treatment-depression-meta/21053988.html
- General References
- Branco JC, Tome AM, Cruz MR, Filipe A: Pirlindole in the treatment of depression and fibromyalgia syndrome. Clin Drug Investig. 2011 Oct 1;31(10):675-89. doi: 10.2165/11595410-000000000-00000. [Article]
- Bruhwyler J, Liegeois JF, Geczy J: Pirlindole: a selective reversible inhibitor of monoamine oxidase A. A review of its preclinical properties. Pharmacol Res. 1997 Jul;36(1):23-33. doi: 10.1006/phrs.1997.0196. [Article]
- Psychiatry: The State of the Art Volume 3 Pharmacopsychiatry [Link]
- Chemistry Dashboard- Pirlindole [Link]
- Pirlindole in the Treatment of Depression and Fibromyalgia Syndrome [Link]
- Hypertensive effect and cheese [Link]
- Monamine oxide inhibitors [Link]
- External Links
- KEGG Drug
- D08392
- PubChem Compound
- 68802
- PubChem Substance
- 310265147
- ChemSpider
- 62039
- ChEBI
- 91755
- ChEMBL
- CHEMBL32350
- Wikipedia
- Pirlindole
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) 145 [L1393] boiling point (°C) 369 [L1393] water solubility 1.68e-02 [L1393] logP 2.80 [L1393] - Predicted Properties
Property Value Source Water Solubility 0.107 mg/mL ALOGPS logP 2.1 ALOGPS logP 3.1 Chemaxon logS -3.3 ALOGPS pKa (Strongest Basic) 8.38 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 16.96 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 70.42 m3·mol-1 Chemaxon Polarizability 27.27 Å3 Chemaxon Number of Rings 4 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 GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0002-0940000000-2e2791b7eaea7b8d12f0 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0090000000-9c15a2184f0d60b04227 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0090000000-d5fbf579d28b739a9230 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0090000000-815991b836571bb81bfe Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0090000000-ba081f19154aa45dc605 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0920000000-eab0da5cda4a497840f7 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-053r-1950000000-b230b01bcc927c8ec605 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]- 157.35458 predictedDeepCCS 1.0 (2019) [M+H]+ 159.71257 predictedDeepCCS 1.0 (2019) [M+Na]+ 165.80573 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Serotonin binding
- Specific Function
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
- Gene Name
- MAOA
- Uniprot ID
- P21397
- Uniprot Name
- Amine oxidase [flavin-containing] A
- Molecular Weight
- 59681.27 Da
References
- Bruhwyler J, Liegeois JF, Geczy J: Pirlindole: a selective reversible inhibitor of monoamine oxidase A. A review of its preclinical properties. Pharmacol Res. 1997 Jul;36(1):23-33. doi: 10.1006/phrs.1997.0196. [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. 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
- Bruhwyler J, Liegeois JF, Geczy J: Pirlindole: a selective reversible inhibitor of monoamine oxidase A. A review of its preclinical properties. Pharmacol Res. 1997 Jul;36(1):23-33. doi: 10.1006/phrs.1997.0196. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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...
- Gene Name
- ADRA2A
- Uniprot ID
- P08913
- Uniprot Name
- Alpha-2A adrenergic receptor
- Molecular Weight
- 48956.275 Da
References
- (r)-pirlindole and its pharmaceutically acceptable salts for use in medicine [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Serotonin binding
- Specific Function
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
- Gene Name
- MAOA
- Uniprot ID
- P21397
- Uniprot Name
- Amine oxidase [flavin-containing] A
- Molecular Weight
- 59681.27 Da
References
- Branco JC, Tome AM, Cruz MR, Filipe A: Pirlindole in the treatment of depression and fibromyalgia syndrome. Clin Drug Investig. 2011 Oct 1;31(10):675-89. doi: 10.2165/11595410-000000000-00000. [Article]
Drug created at October 23, 2015 22:13 / Updated at February 21, 2021 18:52