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Identification
Name Moclobemide
Accession Number DB01171 (APRD00603)
Type small molecule
Groups approved
Description

A reversible monoamine oxidase inhibitor (MAOI) selective for isoform A (RIMA) used to treat major depressive disorder.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
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]
p-Chloro-N-(2-morpholinoethyl)benzamide
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Salts Not Available
Brand names
Name Company
Aurorix
Manerix
Brand mixtures Not Available
Categories
  • Antidepressive Agents
  • Monoamine Oxidase Inhibitors
CAS number 71320-77-9
Weight Average: 268.739
Monoisotopic: 268.097855505
Chemical Formula C13H17ClN2O2
InChI Key InChIKey=YHXISWVBGDMDLQ-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)
Plain Text
IUPAC Name
4-chloro-N-[2-(morpholin-4-yl)ethyl]benzamide
SMILES
ClC1=CC=C(C=C1)C(=O)NCCN1CCOCC1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzoyl Derivatives
  • Benzamides
Substructures
  • Amino Ketones
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Carboxylic Acids and Derivatives
  • Halobenzenes
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Morpholines
  • Benzoyl Derivatives
  • Benzamides
Pharmacology
Indication For the treatment of depression.
Pharmacodynamics 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.
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.
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.
Volume of distribution Not Available
Protein binding Approximately 50% (primarily to albumin)
Metabolism Moclobemide is almost completely metabolized in the liver by Cytochrome P450 2C19 and 2D6.
Route of elimination Not Available
Half life 1-2 hours (4 hours in cirrhotic patients); metabolites are renally excreted
Clearance Not Available
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.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms
Form Route Strength
Tablet Oral
Tablet Oral
Prices
Unit description Cost Unit
Manerix 300 mg Tablet 1.34 USD tablet
Apo-Moclobemide 300 mg Tablet 0.75 USD tablet
Novo-Moclobemide 300 mg Tablet 0.75 USD tablet
Pms-Moclobemide 300 mg Tablet 0.75 USD tablet
Manerix 150 mg Tablet 0.68 USD tablet
Apo-Moclobemide 150 mg Tablet 0.38 USD tablet
Novo-Moclobemide 150 mg Tablet 0.38 USD tablet
Pms-Moclobemide 150 mg Tablet 0.38 USD tablet
Apo-Moclobemide 100 mg Tablet 0.26 USD tablet
Novo-Moclobemide 100 mg Tablet 0.26 USD tablet
Nu-Moclobemide 100 mg Tablet 0.26 USD tablet
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DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
logP 1.5 Not Available
Predicted Properties
Property Value Source
water solubility 1.12e+00 g/l ALOGPS
logP 1.56 ALOGPS
logP 1.45 ChemAxon
logS -2.4 ALOGPS
pKa (strongest acidic) 14.73 ChemAxon
pKa (strongest basic) 6.02 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 41.57 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 71.93 ChemAxon
polarizability 28.28 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D02561 Link_out
PubChem Compound 4235 Link_out
PubChem Substance 46504667 Link_out
ChemSpider 4087 Link_out
BindingDB 15613 Link_out
Therapeutic Targets Database DAP000576 Link_out
PharmGKB PA452615 Link_out
Drug Product Database 2243348 Link_out
Wikipedia http://en.wikipedia.org/wiki/Moclobemide Link_out
ATC Codes
  • N06AG02
AHFS Codes
  • 28:16.04.12
PDB Entries
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Amitriptyline Possible severe adverse reaction with this combination
Amoxapine Possible severe adverse reaction with this combination
Bezafibrate MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like moclobemide.
Brimonidine MAO 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.
Buprenorphine Buprenorphine 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.
Cimetidine Cimetidine 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.
Citalopram Possible serotoninergic syndrome
Clomipramine Possible severe adverse reaction with this combination
Desipramine Possible severe adverse reaction with this combination
Desvenlafaxine Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
Dextromethorphan Increased CNS toxicity
Dobutamine Moclobemide increases the sympathomimetic effect of dobutamine.
Donepezil Possible antagonism of action
Dopamine Moclobemide increases the sympathomimetic effect of dopamine.
Doxepin Possible severe adverse reaction with this combination
Ephedra Moclobemide increases the sympathomimetic effect of ephedra.
Ephedrine Moclobemide increases the sympathomimetic effect of ephedrine.
Epinephrine Moclobemide increases the sympathomimetic effect of epinephrine.
Fenoterol Moclobemide increases the sympathomimetic effect of fenoterol.
Fluoxetine Risk of serotoninergic syndrome
Fluvoxamine Increased incidence of adverse effects with this association
Galantamine Possible antagonism of action
Imipramine Possible severe adverse reaction with this combination
Isoproterenol Moclobemide increases the sympathomimetic effect of isoproterenol.
Meperidine Increased CNS toxicity (can cause death)
Mephentermine Moclobemide increases the sympathomimetic effect of mephentermine.
Metaraminol Moclobemide increases the sympathomimetic effect of metaraminol.
Methoxamine Moclobemide increases the sympathomimetic effect of methoxamine.
Milnacipran Increase serotonin levels. Combination therapy is contraindicated.
Norepinephrine Moclobemide increases the sympathomimetic effect of norepinephrine.
Nortriptyline Possible severe adverse reaction with this combination
Orciprenaline Moclobemide increases the sympathomimetic effect of orciprenaline.
Paroxetine Possible severe adverse reaction with this combination
Phenylephrine Moclobemide increases the sympathomimetic effect of phenylephrine.
Phenylpropanolamine Moclobemide increases the sympathomimetic effect of phenylpropanolamine.
Pirbuterol Moclobemide increases the sympathomimetic effect of pirbuterol.
Procaterol Moclobemide increases the sympathomimetic effect of procaterol.
Protriptyline Possible severe adverse reaction with this combination
Pseudoephedrine Moclobemide increases the sympathomimetic effect of pseudoephedrine.
Rivastigmine Possible antagonism of action
Rizatriptan The MAO inhibitor, moclobemide, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.
Salbutamol Moclobemide increases the sympathomimetic effect of salbutamol.
Selegiline Decrease in selectivity
Sertraline Possible severe adverse reaction with this combination
Sibutramine Possible serotoninergic syndrome with this combination
Tacrine 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.
Terbinafine 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.
Terbutaline Moclobemide increases the sympathomimetic effect of terbutaline.
Tetrabenazine Tetrabenazine may increase the adverse/toxic effects of Moclobemide. Concomitant therapy is contraindicated.
Ticlopidine 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.
Tolcapone 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.
Tramadol Tramadol may increase the risk of serotonin syndrome and seizure induction by the MAO inhibitor, moclobemide.
Tranylcypromine Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trimethobenzamide Trimethobenzamide and Moclobemide, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Trimipramine 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.
Triprolidine 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.
Trospium Trospium and Moclobemide, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Tryptophanyl-5'amp Possible severe adverse reaction with this combination
Venlafaxine Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
Zolmitriptan 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.
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

Pharmacological action: yes
Actions: inhibitor

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 tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine

Organism class: human
UniProt ID: P21397 Link_out
Gene: MAOA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

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 tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine

UniProt ID: P21397 Link_out
Gene: MAOA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

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 tissues. MAOB preferentially degrades benzylamine and phenylethylamine

UniProt ID: P27338 Link_out
Gene: MAOB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor, inducer

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 antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19