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targets (2)
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Identification
Name Isocarboxazid
Accession Number DB01247 (APRD00701)
Type small molecule
Groups approved
Description

An MAO inhibitor that is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in the treatment of panic disorder and the phobic disorders. (From AMA, Drug Evaluations Annual, 1994, p311)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Isocarbonazid
  • Isocarbossazide [Dcit]
  • Isocarboxazida [INN-Spanish]
  • Isocarboxazide
  • Isocarboxazide [INN-French]
  • Isocarboxazidum [INN-Latin]
  • Isocarboxyzid
Brand names
  • Benazide
  • BMIH
  • Enerzer
  • Maraplan
  • Marplan
  • Marplon
Brand name mixtures Not Available
Categories
  • Antidepressants
  • Antidepressive Agents
  • Monoamine Oxidase Inhibitors
CAS number 59-63-2
Weight Average: 231.2505
Monoisotopic: 231.100776675
Chemical Formula C12H13N3O2
InChI Key InChIKey=XKFPYPQQHFEXRZ-UHFFFAOYSA-N
InChI
InChI=1S/C12H13N3O2/c1-9-7-11(15-17-9)12(16)14-13-8-10-5-3-2-4-6-10/h2-7,13H,8H2,1H3,(H,14,16)
Plain Text
IUPAC Name
N'-benzyl-5-methyl-1,2-oxazole-3-carbohydrazide
SMILES
CC1=CC(=NO1)C(=O)NNCC1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzene and Derivatives
Substructures
  • Carboxylic Acids and Derivatives
  • Amino Ketones
  • Benzene and Derivatives
  • Isoxazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Oxazoles
  • Hydrazine Derivatives
  • Imines
Pharmacology
Indication May be used to treat major depressive disorder.
Pharmacodynamics Isocarboxazid is a non-selective hydrazine monoamine oxidase (MAO) inhibitor used to treat depression. In vivo and in vitro studies demonstrated inhibition of MAO in the brain, heart, and liver. Depression is a complicated disease that is not fully understood. It is thought that depression may be linked to an imbalance of chemicals within the brain. When depression occurs, there may be a decrease in the amount of chemicals released from nerve cells in the brain. These chemicals are called monoamines. Monoamines are broken down by a chemical called monoamine oxidase. Isocarboxazid prevents monoamine oxidase from breaking down the monoamines. This results in an increased amount of active monoamines in the brain. By increasing the amount of monoamines in the brain, the imbalance of chemicals thought to be caused by depression is altered. This helps relieve the symptoms of depression.
Mechanism of action Isocarboxazid works by irreversibly blocking the action of a chemical substance known as monoamine oxidase (MAO) in the nervous system. MAO subtypes A and B are involved in the metabolism of serotonin and catecholamine neurotransmitters such as epinephrine, norepinephrine, and dopamine. Isocarboxazid, as a nonselective MAO inhibitor, binds irreversibly to monoamine oxidase–A (MAO-A) and monoamine oxidase–B (MAO-B). The reduced MAO activity results in an increased concentration of these neurotransmitters in storage sites throughout the central nervous system (CNS) and sympathetic nervous system. This increased availability of one or more monoamines is the basis for the antidepressant activity of MAO inhibitors.
Absorption Well absorbed from the gastrointestinal tract.
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Hepatic and rapid (by oxidation).
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Signs of overdose include severe anxiety, confusion, convulsions, cool clammy skin, severe dizziness, severe drowsiness, fast and irregular pulse, fever, hallucinations, severe headache, high or low blood pressure, hyperactive reflexes, muscle stiffness, respiratory depression or failure, slowed reflexes, sweating, severe trouble in sleeping, and unusual irritability.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Validus pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Marplan 10 mg tablet 3.45 USD tablet
Patents Not Available
Properties
State solid
Melting point 105-106 oC
Experimental Properties
Property Value Source
water solubility 1.6 mg/mL at 25 oC [MEYLAN,WM et al. (1996)] PhysProp
logP 2.4 PhysProp
pKa 10.4 Various sources
Predicted Properties
Property Value Source
water solubility 2.24e-01 g/l ALOGPS
logP 1.19 ALOGPS
logP 1.43 ChemAxon Molconvert
logS -3.01 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 67.16 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 74.78 ChemAxon Molconvert
polarizability 24.51 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Kennedy SH, Piran N, Warsh JJ, Prendergast P, Mainprize E, Whynot C, Garfinkel PE: A trial of isocarboxazid in the treatment of bulimia nervosa. J Clin Psychopharmacol. 1988 Dec;8(6):391-6. Pubmed
External Links
Resource Link
KEGG Drug D02580 Link_out
PubChem Compound 3759 Link_out
PubChem Substance 46505330 Link_out
ChemSpider 3628 Link_out
Therapeutic Targets Database DAP000577 Link_out
PharmGKB PA450101 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic/isocarbo.htm Link_out
Drugs.com http://www.drugs.com/cdi/isocarboxazid.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Isocarboxazid Link_out
ATC Codes
  • N06AF01
AHFS Codes Not Available
PDB Entries
FDA label show (56.5 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals, avoid tyramine, caffeine and alcohol.
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. Thase ME, Trivedi MH, Rush AJ: MAOIs in the contemporary treatment of depression. Neuropsychopharmacology. 1995 May;12(3):185-219. Pubmed
  3. Kettler R, Da Prada M, Burkard WP: Comparison of monoamine oxidase-A inhibition by moclobemide in vitro and ex vivo in rats. Acta Psychiatr Scand Suppl. 1990;360:101-2. Pubmed

2. Amine oxidase [flavin-containing] B

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. MAOB preferentially degrades benzylamine and phenylethylamine

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

References:
  1. Mason ST: Chronic administration of type A monoamine oxidase inhibitors increases duration of thiopentone anaesthesia in the rat. Physiol Behav. 1985 Aug;35(2):201-3. Pubmed
  2. Kettler R, Da Prada M, Burkard WP: Comparison of monoamine oxidase-A inhibition by moclobemide in vitro and ex vivo in rats. Acta Psychiatr Scand Suppl. 1990;360:101-2. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:47

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.