Banner
targets (2)
for drugs
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
Salts Not Available
Brand names
Name Company
Benazide
BMIH
Enerzer
Maraplan
Marplan
Marplon
Brand 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
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
melting point 105-106 °C PhysProp
water solubility 1.6 mg/mL at 25 °C MEYLAN,WM et al. (1996)
logP 1.49 HANSCH,C ET AL. (1995)
pKa 10.4 SANGSTER (1994)
Predicted Properties
Property Value Source
water solubility 2.24e-01 g/l ALOGPS
logP 1.19 ALOGPS
logP 1.43 ChemAxon
logS -3 ALOGPS
pKa (strongest acidic) 12.02 ChemAxon
pKa (strongest basic) 3.12 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 67.16 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 74.78 ChemAxon
polarizability 24.51 ChemAxon
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
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
Drug Interaction
Almotriptan The MAO inhibitor, isocarboxazid, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, almotriptan. Concomitant therapy is contraindicated.
Altretamine Risk of severe hypotension
Amitriptyline Possibility of severe adverse effects
Amoxapine Possibility of severe adverse effects
Amphetamine Possible hypertensive crisis
Atomoxetine Possible severe adverse reaction with this combination
Benzphetamine MAO Inhibitors may enhance the hypertensive effect of Amphetamines. Concomitant use of amphetamines and monoamine oxidase inhibitors (MAOI) should be avoided. If used concomitantly, careful monitoring of blood pressure must occur. It may take up to 2 weeks after the discontinuation of an MAOI for the effects to dissipate enough to afford safety to the administration of interacting agents.
Bezafibrate MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like isocarboxazid.
Brimonidine MAO Inhibitors like isocarboxazid 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 isocarboxazid. 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.
Bupropion Possible severe adverse reaction with this combination
Buspirone Possible blood pressure elevation
Citalopram Possible severe adverse reaction with this combination
Clomipramine Possibility of severe adverse effects
Desipramine Possibility of severe adverse effects
Desvenlafaxine Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
Dexfenfluramine Risk of hypertensive crisis.
Dextroamphetamine Possible hypertensive crisis
Dextromethorphan Possible severe adverse reaction
Diethylpropion Possible hypertensive crisis
Dobutamine Increased arterial pressure
Donepezil Possible antagonism of action
Dopamine Increased arterial pressure
Doxepin Possibility of severe adverse effects
Duloxetine Possible severe adverse reaction with this combination
Entacapone Possible hypertensive crisis with this combination
Ephedra Increased arterial pressure
Ephedrine Increased arterial pressure
Epinephrine Increased arterial pressure
Escitalopram Possible severe adverse reaction with this combination
Fenfluramine Possible hypertensive crisis
Fenoterol Increased arterial pressure
Fluoxetine Possible severe adverse reaction with this combination
Fluvoxamine Possible severe adverse reaction with this combination
Galantamine Possible antagonism of action
Guanethidine Isocarboxazid may decrease the effect of guanethidine.
Imipramine Possibility of severe adverse effects
Isoproterenol Increased arterial pressure
L-Tryptophan Possible severe adverse reaction with this combination
Levodopa Possible hypertensive crisis
Mazindol Possible hypertensive crisis
Meperidine Potentially fatal adverse effects
Mephentermine Increased arterial pressure
Metaraminol Increased arterial pressure
Methamphetamine Possible hypertensive crisis
Methotrimeprazine Possible severe adverse reaction with this combination
Methoxamine Increased arterial pressure
Methylphenidate Possible hypertensive crisis with this combination
Midodrine Possible hypertensive crisis with this combination
Milnacipran Increase serotonin levels. Combination therapy is contraindicated.
Mirtazapine Possible severe adverse reaction with this combination
Naratriptan The use of two serotonin modulators increases the risk of serotonin syndrome. Consider alternate therapy or monitor for signs and symptoms of serotonin syndrome.
Nefazodone Possible severe adverse reaction with this combination
Norepinephrine Increased arterial pressure
Nortriptyline Possibility of severe adverse effects
Orciprenaline Increased arterial pressure
Paroxetine Possible severe adverse reaction with this combination
Phendimetrazine Possible hypertensive crisis
Phenmetrazine Possible hypertensive crisis
Phentermine Possible hypertensive crisis
Phenylephrine Increased arterial pressure
Phenylpropanolamine Increased arterial pressure
Pirbuterol Increased arterial pressure
Procaterol Increased arterial pressure
Protriptyline Possibility of severe adverse effects
Pseudoephedrine Increased arterial pressure
Rivastigmine Possible antagonism of action
Rizatriptan The MAO inhibitor, isocarboxazid, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.
Salbutamol Increased arterial pressure
Sertraline Possible severe adverse reaction with this combination
Sibutramine Possible serotoninergic syndrome with this combination
Sumatriptan The MAO inhibitor, isocarboxazid, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, sumatriptan. Concomitant therapy is contraindicated.
Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Isocarboxazid, 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.
Terbutaline Increased arterial pressure
Tetrabenazine Tetrabenazine may increase the adverse/toxic effects of Isocarboxazid. Concomitant therapy is contraindicated.
Tolcapone Tolcapone and Isocarboxazid 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, isocarboxazid.
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 Isocarboxazid, 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 Isocarboxazid, 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 Isocarboxazid, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Venlafaxine Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
Vilazodone MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Avoid combination.
Zolmitriptan The MAO inhibitor, isocarboxazid, may increase the serum concentration of zolmitriptan by decreasing its metabolism. Concomitant therapy and use of zolmitriptan within two weeks of discontinuing isocarboxazid are contraindicated.
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 February 08, 2013 16:20