Drug/Small Molecule:
moclobemide

last updated 08/10/2011

Dutch Pharmacogenetics Working Group Guideline for moclobemide and CYP2C19

Summary

There are currently no dosing recommendations for moclobemide based on CYP2C19 genotype.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for moclobemide based on CYP2C19 genotype [Article:21412232]. They concluded that there are no recommendations at this time.

Phenotype (Genotype) Therapeutic Dose Recommendation Level of Evidence Clinical Relevance
CYP2C19 PM (*2/*2, *2/*3, *3/*3) None Published controlled studies of moderate quality# relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints Minor clinical effect (statistically significant difference): QTc prolongation (<450 ms female, <470 ms male); international normalized ratio increase < 4.5
Kinetic effect (statistically significant difference)
CYP2C19 IM (*1/*2, *1/*3, *17/*2, *17/*3) None no data was retrieved with the literature search no data was retrieved with the literature search
CYP2C19 UM (*17/*17) None no data was retrieved with the literature search no data was retrieved with the literature search

PharmGKB has no annotated drug labels with pharmacogenomic information for this drug/small molecule. If you know of a drug label with PGx, send us a message.

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
Spartan RX CYP2C19 System CYP2C19*17, CYP2C19*2, CYP2C19*3 , rs12248560 , rs4986893 , rs4244285

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all moclobemide variant annotations

Gene ? Variant?
(142)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
VIP No VIP available No VIP available CYP2C19 *2A N/A N/A N/A
VIP No VIP available No VIP available CYP2C19 *3A N/A N/A N/A
rs4244285 24154G>A, 24154G>C, 47346080G>A, 47346080G>C, 681G>A, 681G>C, 96541616G>A, 96541616G>C, CYP2C19*2, CYP2C19:681G>A, CYP2C19:G681A, Pro227=
G > A
G > C
Synonymous
Pro227Pro
rs4986893 22948G>A, 47344874G>A, 636G>A, 96540410G>A, CYP2C19*3, CYP2C19:636G>A, CYP2C19:G636A, Trp212Ter
G > A
Stop Codon
Trp212null
No VIP available No Clinical Annotations available VA
rs6313 102C>T, 160+869C>T, 28449940G>A, 47469940G>A, 6230C>T, HTR2A:102C>T, HTR2A:T102C, Ser34=
G > A
Intronic
Ser34Ser
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 142
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • 4-Chlor-N-(2-morpholinoethyl)benzamid
  • 4-Chloro-N-(2-(4-morpholinyl)ethyl)benzamide
  • 4-Chloro-N-(2-morpholin-4-yl-ethyl)-benzamide
  • Moclaime
  • Moclamide
  • Moclamine
  • Moclobemid
  • Moclobemida [INN-Spanish]
  • Moclobemide [Usan:Ban:Inn]
  • Moclobemidum [INN-Latin]
  • moclobemide
  • p-Chloro-N-(2-morpholinoethyl)benzamide
Trade Names
  • Aurorix
  • Manerix
Brand Mixture Names

PharmGKB Accession Id:
PA452615

Description

A reversible monoamine oxidase inhibitor (MAOI) selective for isoform A (RIMA) used to treat major depressive disorder.

Source: Drug Bank

Indication

For the treatment of depression.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

The mechanism of action of moclobemide involves the selective, reversible inhibition of MAO-A. This inhibition leads to a decrease in the metabolism and destruction of monoamines in the neurotransmitters. This results in an increase in the monoamines, relieving depressive symptoms.

Source: Drug Bank

Pharmacology

Moclobemide belongs to a class of MAOI antidepressants known as reversible inhibitors of monoamine oxidase type-A (RIMAs). The primary role of monoamine oxidase MAO lies in the metabolism of and regulation of the levels of monoamines (serotonin, norepinephrine, and dopamine). Within neurons, MAO appears to regulate the levels of monoamines released upon synaptic firing. Since depression is associated with low levels of monoamines, the inhibition of MAO serves to ease depressive symptoms. RIMAs demonstrate transient inhibition of the substrate binding site of MAO-A as well as competitive displacement from this site by bioamines. The RIMAs are distinguished from the older monoamine oxidase inhibitors (MAOIs) by their selectivity and reversibility.

Source: Drug Bank

Food Interaction

Food slows absorption a little. Avoid alcohol. Take after meals in order to minimize the risk of interaction with tyramine.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Moclobemide is almost completely metabolized in the liver by Cytochrome P450 2C19 and 2D6.

Source: Drug Bank

Protein Binding

Approximately 50% (primarily to albumin)

Source: Drug Bank

Absorption

Well absorbed from the gastrointestinal tract (> 95%). The presence of food reduces the rate but not the extent of absorption. Hepatic first pass metabolism reduces bioavailability to 45-70% following administration of a single dose, but increases to 80% with multiple dosing as a result of saturation of the first pass effect. Peak plasma concentrations are reached within 1 - 2 hours following oral administration.

Source: Drug Bank

Half-Life

1-2 hours (4 hours in cirrhotic patients); metabolites are renally excreted

Source: Drug Bank

Toxicity

LD50 (mouse) is 730mg/kg and LD50 (rat) is 1,300mg/kg. Signs of toxicity include hypertension, drowsiness, dizziness, confusion, tremors, headache, agitation, muscle rigidity and seizures.

Source: Drug Bank

Chemical Properties

Chemical Formula

C13H17ClN2O2

Source: Drug Bank

Isomeric SMILES

c1cc(ccc1C(=O)NCCN2CCOCC2)Cl

Source: OpenEye

Canonical SMILES

ClC1=CC=C(C=C1)C(=O)NCCN1CCOCC1

Source: Drug Bank

Average Molecular Weight

268.739

Source: Drug Bank

Monoisotopic Molecular Weight

268.097855505

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
CYP2C19
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
HTR2A

Drug Targets

Gene Description
MAOA (source: Drug Bank)

Drug Interactions

Drug Description
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Increases the effect of moclobemide (source: Drug Bank)
moclobemide Increases the effect of moclobemide (source: Drug Bank)
moclobemide Possible serotoninergic syndrome (source: Drug Bank)
moclobemide Possible serotoninergic syndrome (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Increased CNS toxicity (source: Drug Bank)
moclobemide Increased CNS toxicity (source: Drug Bank)
moclobemide Possible antagonism of action (source: Drug Bank)
moclobemide Possible antagonism of action (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Moclobemide increases the sympathomimetic effect (source: Drug Bank)
moclobemide Moclobemide increases the sympathomimetic effect of epinephrine. (source: Drug Bank)
moclobemide Moclobemide increases the sympathomimetic effect (source: Drug Bank)
moclobemide Moclobemide increases the sympathomimetic effect of fenoterol. (source: Drug Bank)
moclobemide Risk of serotoninergic syndrome (source: Drug Bank)
moclobemide Risk of serotoninergic syndrome (source: Drug Bank)
moclobemide Increased incidence of adverse effects with this association (source: Drug Bank)
moclobemide Increased incidence of adverse effects with this association (source: Drug Bank)
moclobemide Possible antagonism of action (source: Drug Bank)
moclobemide Possible antagonism of action (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Increased CNS toxicity (can cause death) (source: Drug Bank)
moclobemide Increased CNS toxicity (can cause death) (source: Drug Bank)
amitriptyline Possible severe adverse reaction with this combination (source: Drug Bank)
amitriptyline Possible severe adverse reaction with this combination (source: Drug Bank)
amoxapine Possible severe adverse reaction with this combination (source: Drug Bank)
amoxapine Possible severe adverse reaction with this combination (source: Drug Bank)
cimetidine Cimetidine increases the effect of moclobemide (source: Drug Bank)
cimetidine Cimetidine increases the effect of moclobemide (source: Drug Bank)
citalopram Possible serotoninergic syndrome (source: Drug Bank)
citalopram Possible serotoninergic syndrome (source: Drug Bank)
clomipramine Possible severe adverse reaction with this combination (source: Drug Bank)
clomipramine Possible severe adverse reaction with this combination (source: Drug Bank)
desipramine Possible severe adverse reaction with this combination (source: Drug Bank)
desipramine Possible severe adverse reaction with this combination (source: Drug Bank)
dextromethorphan Increased CNS toxicity (source: Drug Bank)
dextromethorphan Increased CNS toxicity (source: Drug Bank)
dobutamine Moclobemide increases the sympathomimetic effect (source: Drug Bank)
dobutamine Moclobemide increases the sympathomimetic effect of dobutamine. (source: Drug Bank)
donepezil Possible antagonism of action (source: Drug Bank)
donepezil Possible antagonism of action (source: Drug Bank)
dopamine Moclobemide increases the sympathomimetic effect (source: Drug Bank)
dopamine Moclobemide increases the sympathomimetic effect of dopamine. (source: Drug Bank)
doxepin Possible severe adverse reaction with this combination (source: Drug Bank)
doxepin Possible severe adverse reaction with this combination (source: Drug Bank)
ephedra Moclobemide increases the sympathomimetic effect of ephedra. (source: Drug Bank)
ephedrine Moclobemide increases the sympathomimetic effect (source: Drug Bank)
ephedrine Moclobemide increases the sympathomimetic effect of ephedrine. (source: Drug Bank)
epinephrine Moclobemide increases the sympathomimetic effect (source: Drug Bank)
epinephrine Moclobemide increases the sympathomimetic effect of epinephrine. (source: Drug Bank)
fenoterol Moclobemide increases the sympathomimetic effect (source: Drug Bank)
fenoterol Moclobemide increases the sympathomimetic effect of fenoterol. (source: Drug Bank)
fluoxetine Risk of serotoninergic syndrome (source: Drug Bank)
fluoxetine Risk of serotoninergic syndrome (source: Drug Bank)
fluvoxamine Increased incidence of adverse effects with this association (source: Drug Bank)
fluvoxamine Increased incidence of adverse effects with this association (source: Drug Bank)
galantamine Possible antagonism of action (source: Drug Bank)
galantamine Possible antagonism of action (source: Drug Bank)
imipramine Possible severe adverse reaction with this combination (source: Drug Bank)
imipramine Possible severe adverse reaction with this combination (source: Drug Bank)
isoproterenol Moclobemide increases the sympathomimetic effect (source: Drug Bank)
isoproterenol Moclobemide increases the sympathomimetic effect of isoproterenol. (source: Drug Bank)
meperidine Increased CNS toxicity (can cause death) (source: Drug Bank)
meperidine Increased CNS toxicity (can cause death) (source: Drug Bank)
mephentermine Moclobemide increases the sympathomimetic effect of mephentermine. (source: Drug Bank)
metaraminol Moclobemide increases the sympathomimetic effect of metaraminol. (source: Drug Bank)
methoxamine Moclobemide increases the sympathomimetic effect (source: Drug Bank)
methoxamine Moclobemide increases the sympathomimetic effect of methoxamine. (source: Drug Bank)
norepinephrine Moclobemide increases the sympathomimetic effect (source: Drug Bank)
norepinephrine Moclobemide increases the sympathomimetic effect of norepinephrine. (source: Drug Bank)
nortriptyline Possible severe adverse reaction with this combination (source: Drug Bank)
nortriptyline Possible severe adverse reaction with this combination (source: Drug Bank)
orciprenaline Moclobemide increases the sympathomimetic effect (source: Drug Bank)
orciprenaline Moclobemide increases the sympathomimetic effect of orciprenaline. (source: Drug Bank)
paroxetine Possible severe adverse reaction with this combination (source: Drug Bank)
paroxetine Possible severe adverse reaction with this combination (source: Drug Bank)
phenylephrine Moclobemide increases the sympathomimetic effect (source: Drug Bank)
phenylephrine Moclobemide increases the sympathomimetic effect of phenylephrine. (source: Drug Bank)
phenylpropanolamine Moclobemide increases the sympathomimetic effect of phenylpropanolamine. (source: Drug Bank)
pirbuterol Moclobemide increases the sympathomimetic effect (source: Drug Bank)
pirbuterol Moclobemide increases the sympathomimetic effect of pirbuterol. (source: Drug Bank)
procaterol Moclobemide increases the sympathomimetic effect of procaterol. (source: Drug Bank)
protriptyline Possible severe adverse reaction with this combination (source: Drug Bank)
protriptyline Possible severe adverse reaction with this combination (source: Drug Bank)
pseudoephedrine Moclobemide increases the sympathomimetic effect (source: Drug Bank)
pseudoephedrine Moclobemide increases the sympathomimetic effect of pseudoephedrine. (source: Drug Bank)
rivastigmine Possible antagonism of action (source: Drug Bank)
rivastigmine Possible antagonism of action (source: Drug Bank)
rizatriptan The MAO inhibitor increases the effect and toxicity of rizatriptan (source: Drug Bank)
rizatriptan The MAO inhibitor increases the effect and toxicity of rizatriptan (source: Drug Bank)
salbutamol Moclobemide increases the sympathomimetic effect (source: Drug Bank)
salbutamol Moclobemide increases the sympathomimetic effect of salbutamol. (source: Drug Bank)
selegiline Decrease in selectivity (source: Drug Bank)
selegiline Decrease in selectivity (source: Drug Bank)
sertraline Possible severe adverse reaction with this combination (source: Drug Bank)
sertraline Possible severe adverse reaction with this combination (source: Drug Bank)
sibutramine Possible serotoninergic syndrome with this combination (source: Drug Bank)
sibutramine Possible serotoninergic syndrome with this combination (source: Drug Bank)
terbutaline Moclobemide increases the sympathomimetic effect (source: Drug Bank)
terbutaline Moclobemide increases the sympathomimetic effect of terbutaline. (source: Drug Bank)
tramadol Increased risk of seizures and serotonin syndrome (source: Drug Bank)
tramadol Increased risk of seizures and serotonin syndrome (source: Drug Bank)
tramadol Increased risk of seizures and serotonin syndrome (source: Drug Bank)
trimipramine Possible severe adverse reaction with this combination (source: Drug Bank)
trimipramine Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Moclobemide increases the sympathomimetic effect (source: Drug Bank)
moclobemide Moclobemide increases the sympathomimetic effect of orciprenaline. (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Moclobemide increases the sympathomimetic effect (source: Drug Bank)
moclobemide Moclobemide increases the sympathomimetic effect of phenylephrine. (source: Drug Bank)
moclobemide Moclobemide increases the sympathomimetic effect of phenylpropanolamine. (source: Drug Bank)
moclobemide Moclobemide increases the sympathomimetic effect (source: Drug Bank)
moclobemide Moclobemide increases the sympathomimetic effect of pseudoephedrine. (source: Drug Bank)
moclobemide The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Moclobemide, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents. (source: Drug Bank)
moclobemide The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Moclobemide, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents. (source: Drug Bank)
moclobemide Terbinafine may reduce the metabolism and clearance of Moclobemide. Consider alternate therapy or monitor for therapeutic/adverse effects of Moclobemide if Terbinafine is initiated, discontinued or dose changed. (source: Drug Bank)
moclobemide Moclobemide increases the sympathomimetic effect (source: Drug Bank)
moclobemide Moclobemide increases the sympathomimetic effect of terbutaline. (source: Drug Bank)
moclobemide Tetrabenazine may increase the adverse/toxic effects of Moclobemide. Concomitant therapy is contraindicated. (source: Drug Bank)
moclobemide Ticlopidine may decrease the metabolism and clearance of Moclobemide. Consider alternate therapy or monitor for adverse/toxic effects of Moclobemide if Ticlopidine is initiated, discontinued or dose changed. (source: Drug Bank)
moclobemide Tolcapone and Moclobemide decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects. (source: Drug Bank)
moclobemide Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Moclobemide. (source: Drug Bank)
moclobemide Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome. (source: Drug Bank)
moclobemide Increased risk of serotonin syndrome. The 2D6 inhibitor, Trazodone, may also increase the efficacy of Moclobemide by decreasing Moclobemide metabolism and clearance. Monitor for symptoms of serotonin syndrome and changes in Moclobemide efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank)
moclobemide Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank)
moclobemide Trimethobenzamide and Moclobemide, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank)
moclobemide Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis. (source: Drug Bank)
moclobemide Triprolidine and Moclobemide, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects. (source: Drug Bank)
moclobemide Triprolidine and Moclobemide, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects. (source: Drug Bank)
moclobemide Trospium and Moclobemide, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank)
moclobemide Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided. (source: Drug Bank)
moclobemide The MAO inhibitor, moclobemide, may increase the serum concentration of zolmitriptan by decreasing its metabolism. Concomitant therapy and use of zolmitriptan within two weeks of discontinuing moclobemide are contraindicated. (source: Drug Bank)

Curated Information ?

EvidenceDisease
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Overdose
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Serotonin Syndrome

Publications related to moclobemide: 3

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Serotonin toxicity from antidepressant overdose and its association with the T102C polymorphism of the 5-HT2A receptor. The pharmacogenomics journal. 2014. Cooper J M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 19. Pharmacogenetics and genomics. 2011. Scott Stuart A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Drug metabolism genotypes and their association with adverse drug reactions in selected populations: a pilot study of methodology. Pharmacoepidemiology and drug safety. 2000. Clark D, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01171
KEGG Drug:
D02561
PubChem Compound:
4235
PubChem Substance:
189524
46504667
Drugs Product Database (DPD):
2243348
BindingDB:
15613
ChemSpider:
4087
Therapeutic Targets Database:
DAP000576

Clinical Trials

These are trials that mention moclobemide and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.