You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameMoclobemide
Accession NumberDB01171  (APRD00603)
TypeSmall Molecule
GroupsApproved
Description

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

Structure
Thumb
Synonyms
SynonymLanguageCode
4-Chlor-N-(2-morpholinoethyl)benzamidNot AvailableNot Available
4-Chloro-N-(2-(4-morpholinyl)ethyl)benzamideNot AvailableNot Available
4-Chloro-N-(2-morpholin-4-yl-ethyl)-benzamideNot AvailableNot Available
AurorixNot AvailableNot Available
MoclaimeNot AvailableNot Available
MoclamideNot AvailableNot Available
MoclamineNot AvailableNot Available
MoclobemidNot AvailableNot Available
MoclobemidaSpanishINN
MoclobemideNot AvailableINN, BAN, USAN
MoclobemidumLatinINN
p-Chloro-N-(2-morpholinoethyl)benzamideNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AurorixNot Available
ManerixNot Available
Brand mixturesNot Available
Categories
CAS number71320-77-9
WeightAverage: 268.739
Monoisotopic: 268.097855505
Chemical FormulaC13H17ClN2O2
InChI KeyYHXISWVBGDMDLQ-UHFFFAOYSA-N
InChI
InChI=1S/C13H17ClN2O2/c14-12-3-1-11(2-4-12)13(17)15-5-6-16-7-9-18-10-8-16/h1-4H,5-10H2,(H,15,17)
IUPAC Name
4-chloro-N-[2-(morpholin-4-yl)ethyl]benzamide
SMILES
ClC1=CC=C(C=C1)C(=O)NCCN1CCOCC1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzamides
Direct parentBenzamides
Alternative parentsBenzoyl Derivatives; Chlorobenzenes; Aryl Chlorides; Morpholines; Tertiary Amines; Secondary Carboxylic Acid Amides; Enolates; Ethers; Carboxylic Acids; Polyamines; Organochlorides
Substituentsbenzoyl; chlorobenzene; aryl chloride; aryl halide; oxazinane; morpholine; secondary carboxylic acid amide; tertiary amine; carboxamide group; polyamine; carboxylic acid derivative; ether; enolate; carboxylic acid; organochloride; organohalogen; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzamides. These are organic compounds containing a carboxamido substituent attached to a benzene ring.
Pharmacology
IndicationFor the treatment of depression.
PharmacodynamicsMoclobemide 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.
Mechanism of actionThe 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.
AbsorptionWell 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.
Volume of distributionNot Available
Protein bindingApproximately 50% (primarily to albumin)
Metabolism

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

Route of eliminationNot Available
Half life1-2 hours (4 hours in cirrhotic patients); metabolites are renally excreted
ClearanceNot Available
ToxicityLD50 (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.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9838
Blood Brain Barrier + 0.9691
Caco-2 permeable - 0.5602
P-glycoprotein substrate Substrate 0.6652
P-glycoprotein inhibitor I Inhibitor 0.6892
P-glycoprotein inhibitor II Non-inhibitor 0.8637
Renal organic cation transporter Non-inhibitor 0.5691
CYP450 2C9 substrate Non-substrate 0.8538
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.5723
CYP450 1A2 substrate Non-inhibitor 0.9138
CYP450 2C9 substrate Non-inhibitor 0.8989
CYP450 2D6 substrate Non-inhibitor 0.8081
CYP450 2C19 substrate Inhibitor 0.8024
CYP450 3A4 substrate Non-inhibitor 0.9384
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5956
Ames test Non AMES toxic 0.6867
Carcinogenicity Non-carcinogens 0.8727
Biodegradation Not ready biodegradable 0.9844
Rat acute toxicity 2.6098 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7135
hERG inhibition (predictor II) Inhibitor 0.5646
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
TabletOral
Prices
Unit descriptionCostUnit
Manerix 300 mg Tablet1.34USDtablet
Apo-Moclobemide 300 mg Tablet0.75USDtablet
Novo-Moclobemide 300 mg Tablet0.75USDtablet
Pms-Moclobemide 300 mg Tablet0.75USDtablet
Manerix 150 mg Tablet0.68USDtablet
Apo-Moclobemide 150 mg Tablet0.38USDtablet
Novo-Moclobemide 150 mg Tablet0.38USDtablet
Pms-Moclobemide 150 mg Tablet0.38USDtablet
Apo-Moclobemide 100 mg Tablet0.26USDtablet
Novo-Moclobemide 100 mg Tablet0.26USDtablet
Nu-Moclobemide 100 mg Tablet0.26USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP1.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.12ALOGPS
logP1.56ALOGPS
logP1.45ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)14.73ChemAxon
pKa (Strongest Basic)6.02ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area41.57 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity71.93 m3·mol-1ChemAxon
Polarizability28.28 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD02561
PubChem Compound4235
PubChem Substance46504667
ChemSpider4087
BindingDB15613
Therapeutic Targets DatabaseDAP000576
PharmGKBPA452615
Drug Product Database2243348
WikipediaMoclobemide
ATC CodesN06AG02
AHFS Codes
  • 28:16.04.12
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AmitriptylinePossible severe adverse reaction with this combination
AmoxapinePossible severe adverse reaction with this combination
BezafibrateMAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like moclobemide.
BrimonidineMAO Inhibitors like moclobemide may enhance the hypertensive effect of Alpha2-Agonists (Ophthalmic). The concomitant use of monoamine oxidase inhibitors and ophthalmic alpha2 agonists is contraindicated.
BuprenorphineBuprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like moclobemide. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.
CimetidineCimetidine may increase the serum concentration of moclobemide by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of moclobemide if cimetidine is initiated, discontinued or dose changed.
CitalopramPossible serotoninergic syndrome
ClomipraminePossible severe adverse reaction with this combination
DesipraminePossible severe adverse reaction with this combination
DesvenlafaxineIncreased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
DextromethorphanIncreased CNS toxicity
DobutamineMoclobemide increases the sympathomimetic effect of dobutamine.
DonepezilPossible antagonism of action
DopamineMoclobemide increases the sympathomimetic effect of dopamine.
DoxepinPossible severe adverse reaction with this combination
EphedraMoclobemide increases the sympathomimetic effect of ephedra.
EphedrineMoclobemide increases the sympathomimetic effect of ephedrine.
EpinephrineMoclobemide increases the sympathomimetic effect of epinephrine.
FenoterolMoclobemide increases the sympathomimetic effect of fenoterol.
FluoxetineRisk of serotoninergic syndrome
FluvoxamineIncreased incidence of adverse effects with this association
GalantaminePossible antagonism of action
ImipraminePossible severe adverse reaction with this combination
IsoprenalineMoclobemide increases the sympathomimetic effect of isoproterenol.
MephentermineMoclobemide increases the sympathomimetic effect of mephentermine.
MetaraminolMoclobemide increases the sympathomimetic effect of metaraminol.
MethoxamineMoclobemide increases the sympathomimetic effect of methoxamine.
MilnacipranIncrease serotonin levels. Combination therapy is contraindicated.
NorepinephrineMoclobemide increases the sympathomimetic effect of norepinephrine.
NortriptylinePossible severe adverse reaction with this combination
OrciprenalineMoclobemide increases the sympathomimetic effect of orciprenaline.
ParoxetinePossible severe adverse reaction with this combination
PethidineIncreased CNS toxicity (can cause death)
PhenylephrineMoclobemide increases the sympathomimetic effect of phenylephrine.
PhenylpropanolamineMoclobemide increases the sympathomimetic effect of phenylpropanolamine.
PirbuterolMoclobemide increases the sympathomimetic effect of pirbuterol.
ProcaterolMoclobemide increases the sympathomimetic effect of procaterol.
ProtriptylinePossible severe adverse reaction with this combination
PseudoephedrineMoclobemide increases the sympathomimetic effect of pseudoephedrine.
RivastigminePossible antagonism of action
RizatriptanThe MAO inhibitor, moclobemide, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.
SalbutamolMoclobemide increases the sympathomimetic effect of salbutamol.
SelegilineDecrease in selectivity
SertralinePossible severe adverse reaction with this combination
SibutraminePossible serotoninergic syndrome with this combination
TacrineThe 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.
TerbinafineTerbinafine 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.
TerbutalineMoclobemide increases the sympathomimetic effect of terbutaline.
TetrabenazineTetrabenazine may increase the adverse/toxic effects of Moclobemide. Concomitant therapy is contraindicated.
TiclopidineTiclopidine 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.
TolcaponeTolcapone 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.
TramadolTramadol may increase the risk of serotonin syndrome and seizure induction by the MAO inhibitor, moclobemide.
TranylcypromineIncreased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
TrazodoneIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TrimethobenzamideTrimethobenzamide and Moclobemide, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
TrimipramineIncreased 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.
TriprolidineTriprolidine 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.
TrospiumTrospium and Moclobemide, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Tryptophanyl-5'ampPossible severe adverse reaction with this combination
VenlafaxineIncreased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
ZolmitriptanThe 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.
Food Interactions
  • Food slows absorption a little. Avoid alcohol. Take after meals in order to minimize the risk of interaction with tyramine.

Targets

1. Amine oxidase [flavin-containing] A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Amine oxidase [flavin-containing] A P21397 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Berlin I, Zimmer R, Thiede HM, Payan C, Hergueta T, Robin L, Puech AJ: Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase-A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects. Br J Clin Pharmacol. 1990 Dec;30(6):805-16. Pubmed
  3. Fulton B, Benfield P: Moclobemide. An update of its pharmacological properties and therapeutic use. Drugs. 1996 Sep;52(3):450-74. Pubmed

Enzymes

1. Amine oxidase [flavin-containing] A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Amine oxidase [flavin-containing] A P21397 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Amine oxidase [flavin-containing] B

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Amine oxidase [flavin-containing] B P27338 Details

References:

  1. Fisar Z, Hroudova J, Raboch J: Inhibition of monoamine oxidase activity by antidepressants and mood stabilizers. Neuro Endocrinol Lett. 2010;31(5):645-56. Pubmed

3. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13