Pirlindole

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
Thumb
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.

Pharmacology
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:
Machine Learning
Data Science
Drug Discovery
Accelerate your drug discovery research with our fully connected ADMET dataset
Learn more
Contraindications & Blackbox Warnings
Contraindications
Contraindications & Blackbox Warnings
With our commercial data, access important information on dangerous risks, contraindications, and adverse effects.
Learn more
Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects
Learn more
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.

TargetActionsOrganism
UAmine oxidase [flavin-containing] A
antagonist
Humans
U5-hydroxytryptamine receptor 1A
antagonist
Humans
UAlpha-2A adrenergic receptor
antagonist
Humans
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
Medicalerrors
Reduce medical errors
and improve treatment outcomes with our comprehensive & structured data on drug adverse effects.
Learn more
Reduce medical errors & improve treatment outcomes with our adverse effects data
Learn more
Toxicity

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
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when Pirlindole is combined with 1,2-Benzodiazepine.
AbacavirAbacavir may decrease the excretion rate of Pirlindole which could result in a higher serum level.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Pirlindole is combined with Abciximab.
AcarbosePirlindole may increase the hypoglycemic activities of Acarbose.
AcebutololPirlindole may increase the hypotensive activities of Acebutolol.
AceclofenacAceclofenac may decrease the excretion rate of Pirlindole which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Pirlindole which could result in a higher serum level.
AcenocoumarolThe risk or severity of bleeding and hemorrhage can be increased when Pirlindole is combined with Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Pirlindole which could result in a higher serum level.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Pirlindole.
Interactions
Improve patient outcomes
Build effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.
Learn more
Food Interactions
Not Available

Products

Products
Comprehensive & structured drug product info
From application numbers to product codes, connect different identifiers through our commercial datasets.
Learn more
Easily connect various identifiers back to our datasets
Learn more
Product Ingredients
IngredientUNIICASInChI Key
Pirlindole hydrochlorideQ89W8I397C16154-78-2LIFOOCLGAAEVIF-UHFFFAOYSA-N
Pirlindole lactatePRE19MC9Y9292039-20-4PXRNCRKTECAYRB-UHFFFAOYSA-N

Categories

Drug Categories
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
  1. 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]
  2. 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]
  3. Psychiatry: The State of the Art Volume 3 Pharmacopsychiatry [Link]
  4. Chemistry Dashboard- Pirlindole [Link]
  5. Pirlindole in the Treatment of Depression and Fibromyalgia Syndrome [Link]
  6. Hypertensive effect and cheese [Link]
  7. Monamine oxide inhibitors [Link]
KEGG Drug
D08392
PubChem Compound
68802
PubChem Substance
310265147
ChemSpider
62039
ChEBI
91755
ChEMBL
CHEMBL32350
Wikipedia
Pirlindole

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)145 [L1393]
boiling point (°C)369 [L1393]
water solubility1.68e-02[L1393]
logP2.80[L1393]
Predicted Properties
PropertyValueSource
Water Solubility0.107 mg/mLALOGPS
logP2.1ALOGPS
logP3.1ChemAxon
logS-3.3ALOGPS
pKa (Strongest Basic)8.38ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area16.96 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity70.42 m3·mol-1ChemAxon
Polarizability27.27 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets
Accelerate your drug discovery research
with our fully connected ADMET & drug target dataset.
Learn more
Accelerate your drug discovery research with our ADMET & drug target dataset
Learn more
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
  1. 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
  1. 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
  1. (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
  1. 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 on October 23, 2015 22:13 / Updated on February 21, 2021 18:52