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Identification
NameIsocarboxazid
Accession NumberDB01247  (APRD00701)
TypeSmall Molecule
GroupsApproved
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
Synonyms
Isocarboxazida
Isocarboxazide
Isocarboxazidum
Marplan
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Marplantablet10 mg/1oralValidus Pharmaceuticals LLC1959-07-01Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
EnerzerTakeda
IsocarboxazidAlliance
Brand mixturesNot Available
SaltsNot Available
Categories
UNII34237V843T
CAS number59-63-2
WeightAverage: 231.2505
Monoisotopic: 231.100776675
Chemical FormulaC12H13N3O2
InChI KeyInChIKey=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)
IUPAC Name
N'-benzyl-5-methyl-1,2-oxazole-3-carbohydrazide
SMILES
CC1=CC(=NO1)C(=O)NNCC1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylmethylamines. These are compounds containing a phenylmethtylamine moiety, which consists of a phenyl group substituted by an methanamine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylmethylamines
Direct ParentPhenylmethylamines
Alternative Parents
Substituents
  • Phenylmethylamine
  • Benzylamine
  • Heteroaromatic compound
  • Oxazole
  • Isoxazole
  • Azole
  • Carboxylic acid hydrazide
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationMay be used to treat major depressive disorder.
PharmacodynamicsIsocarboxazid 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 actionIsocarboxazid 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.
Related Articles
AbsorptionWell absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic and rapid (by oxidation).

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySigns 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9783
Caco-2 permeable-0.5531
P-glycoprotein substrateNon-substrate0.6987
P-glycoprotein inhibitor INon-inhibitor0.9138
P-glycoprotein inhibitor IINon-inhibitor0.9716
Renal organic cation transporterNon-inhibitor0.8247
CYP450 2C9 substrateNon-substrate0.8471
CYP450 2D6 substrateNon-substrate0.8141
CYP450 3A4 substrateNon-substrate0.6057
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8885
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8518
Ames testAMES toxic0.5973
CarcinogenicityCarcinogens 0.5
BiodegradationNot ready biodegradable0.9227
Rat acute toxicity2.9486 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9209
hERG inhibition (predictor II)Non-inhibitor0.9069
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral10 mg/1
Prices
Unit descriptionCostUnit
Marplan 10 mg tablet3.45USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point105-106 °CU.S. Patent 2,908,688.
water solubility1.6 mg/mL at 25 °CMEYLAN,WM et al. (1996)
logP1.49HANSCH,C ET AL. (1995)
pKa10.4SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.224 mg/mLALOGPS
logP1.19ALOGPS
logP1.43ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)12.02ChemAxon
pKa (Strongest Basic)3.12ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area67.16 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity74.78 m3·mol-1ChemAxon
Polarizability24.51 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-0006-9500000000-6ab30f52fc69889b3fa2View in MoNA
References
Synthesis Reference

U.S. Patent 2,908,688.

General References
  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:3069879 ]
External Links
ATC CodesN06AF01
AHFS CodesNot Available
PDB Entries
FDA labelDownload (56.5 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcepromazineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Acepromazine.
AcetophenazineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Acetophenazine.
AclidiniumAclidinium may increase the anticholinergic activities of Isocarboxazid.
AltretamineAltretamine may increase the orthostatic hypotensive activities of Isocarboxazid.
AmisulprideThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Amisulpride.
AmitriptylineIsocarboxazid may increase the serotonergic activities of Amitriptyline.
AmphetamineIsocarboxazid may increase the hypertensive activities of Amphetamine.
ApraclonidineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Apraclonidine.
AripiprazoleThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Aripiprazole.
AtomoxetineIsocarboxazid may increase the central neurotoxic activities of Atomoxetine.
AtropineIsocarboxazid may increase the hypertensive activities of Atropine.
BenzquinamideThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Benzquinamide.
BetahistineThe serum concentration of Betahistine can be increased when it is combined with Isocarboxazid.
BezafibrateThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Bezafibrate.
Botulinum Toxin Type AIsocarboxazid may increase the anticholinergic activities of Botulinum Toxin Type A.
Botulinum Toxin Type BIsocarboxazid may increase the anticholinergic activities of Botulinum Toxin Type B.
BrimonidineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Brimonidine.
BuprenorphineThe risk or severity of adverse effects can be increased when Buprenorphine is combined with Isocarboxazid.
BupropionIsocarboxazid may increase the hypertensive activities of Bupropion.
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Isocarboxazid.
CarbamazepineThe risk or severity of adverse effects can be increased when Carbamazepine is combined with Isocarboxazid.
CarphenazineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Carphenazine.
CathinoneIsocarboxazid may increase the hypertensive activities of Cathinone.
ChlormezanoneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Chlormezanone.
ChlorpromazineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Chlorpromazine.
ChlorprothixeneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Chlorprothixene.
Cimetropium BromideIsocarboxazid may increase the anticholinergic activities of Cimetropium Bromide.
ClemastineIsocarboxazid may increase the anticholinergic activities of Clemastine.
ClozapineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Clozapine.
CyclobenzaprineCyclobenzaprine may increase the serotonergic activities of Isocarboxazid.
CyproheptadineIsocarboxazid may increase the anticholinergic activities of Cyproheptadine.
DapoxetineThe risk or severity of adverse effects can be increased when Dapoxetine is combined with Isocarboxazid.
DexmethylphenidateIsocarboxazid may increase the hypertensive activities of Dexmethylphenidate.
DextromethorphanIsocarboxazid may increase the serotonergic activities of Dextromethorphan.
DiethylpropionIsocarboxazid may increase the hypertensive activities of Diethylpropion.
DomperidoneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Domperidone.
DoxapramIsocarboxazid may increase the hypertensive activities of Doxapram.
DoxylamineIsocarboxazid may increase the anticholinergic activities of Doxylamine.
DronabinolIsocarboxazid may increase the tachycardic activities of Dronabinol.
DroperidolThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Droperidol.
EluxadolineIsocarboxazid may increase the activities of Eluxadoline.
EpinephrineIsocarboxazid may increase the hypertensive activities of Epinephrine.
EthanolThe risk or severity of adverse effects can be increased when Ethanol is combined with Isocarboxazid.
FencamfamineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Fencamfamine.
FlupentixolThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Flupentixol.
FluphenazineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Fluphenazine.
FluspirileneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Fluspirilene.
FluvoxamineThe risk or severity of adverse effects can be increased when Fluvoxamine is combined with Isocarboxazid.
Glucagon recombinantThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Glucagon recombinant.
GranisetronGranisetron may increase the serotonergic activities of Isocarboxazid.
HaloperidolThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Haloperidol.
HydrocodoneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Hydrocodone.
HydromorphoneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Hydromorphone.
Insulin HumanIsocarboxazid may increase the hypoglycemic activities of Insulin Regular.
Ipratropium bromideIpratropium bromide may increase the anticholinergic activities of Isocarboxazid.
IsomethepteneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Isometheptene.
ItoprideThe therapeutic efficacy of Itopride can be decreased when used in combination with Isocarboxazid.
L-TryptophanThe risk or severity of adverse effects can be increased when L-Tryptophan is combined with Isocarboxazid.
LevodopaThe risk or severity of adverse effects can be increased when Levodopa is combined with Isocarboxazid.
LevonordefrinIsocarboxazid may increase the hypertensive activities of Levonordefrin.
LinezolidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Linezolid.
LithiumThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Lithium.
LoxapineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Loxapine.
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Isocarboxazid.
MequitazineIsocarboxazid may increase the anticholinergic activities of Mequitazine.
MesoridazineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Mesoridazine.
MethadoneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Methadone.
MethotrimeprazineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Methotrimeprazine.
MethyldopaThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Methyldopa.
Methylene blueIsocarboxazid may increase the serotonergic activities of Methylene blue.
MethylphenidateIsocarboxazid may increase the hypertensive activities of Methylphenidate.
MetoclopramideThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Metoclopramide.
MianserinIsocarboxazid may increase the neurotoxic activities of Mianserin.
MidodrineIsocarboxazid may increase the hypertensive activities of Midodrine.
MirabegronThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Mirabegron.
MirtazapineIsocarboxazid may increase the central neurotoxic activities of Mirtazapine.
MoclobemideThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Moclobemide.
MolindoneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Molindone.
MorphineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Morphine.
MoxonidineIsocarboxazid may increase the hypotensive activities of Moxonidine.
NorepinephrineIsocarboxazid may increase the hypertensive activities of Norepinephrine.
OlanzapineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Olanzapine.
OndansetronThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Ondansetron.
OrciprenalineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Orciprenaline.
OxycodoneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Oxycodone.
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Isocarboxazid.
PaliperidoneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Paliperidone.
ParoxetineIsocarboxazid may increase the serotonergic activities of Paroxetine.
PerphenazineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Perphenazine.
PethidineIsocarboxazid may increase the serotonergic activities of Pethidine.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Isocarboxazid.
PholcodinePholcodine may increase the serotonergic activities of Isocarboxazid.
PimozideThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Pimozide.
PiperacetazineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Piperacetazine.
PizotifenIsocarboxazid may increase the anticholinergic activities of Pizotifen.
Potassium ChlorideIsocarboxazid may increase the ulcerogenic activities of Potassium Chloride.
PramlintidePramlintide may increase the anticholinergic activities of Isocarboxazid.
ProchlorperazineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Prochlorperazine.
ProcyclidineThe risk or severity of adverse effects can be increased when Procyclidine is combined with Isocarboxazid.
PromazineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Promazine.
QuetiapineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Quetiapine.
RamosetronIsocarboxazid may increase the activities of Ramosetron.
RemoxiprideThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Remoxipride.
ReserpineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Reserpine.
RisperidoneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Risperidone.
SecretinThe therapeutic efficacy of Secretin can be decreased when used in combination with Isocarboxazid.
SertindoleThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Sertindole.
SufentanilSufentanil may increase the serotonergic activities of Isocarboxazid.
SulpirideThe therapeutic efficacy of Sulpiride can be decreased when used in combination with Isocarboxazid.
TacrineThe therapeutic efficacy of Isocarboxazid can be decreased when used in combination with Tacrine.
TapentadolThe risk or severity of adverse effects can be increased when Tapentadol is combined with Isocarboxazid.
Tedizolid PhosphateTedizolid Phosphate may increase the serotonergic activities of Isocarboxazid.
TetrabenazineThe risk or severity of adverse effects can be increased when Tetrabenazine is combined with Isocarboxazid.
TetryzolineIsocarboxazid may increase the hypertensive activities of Tetryzoline.
ThioridazineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Thioridazine.
ThiothixeneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Thiothixene.
TianeptineThe risk or severity of adverse effects can be increased when Tianeptine is combined with Isocarboxazid.
TiotropiumIsocarboxazid may increase the anticholinergic activities of Tiotropium.
TolcaponeThe risk or severity of adverse effects can be increased when Tolcapone is combined with Isocarboxazid.
TopiramateThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Topiramate.
TramadolTramadol may increase the neuroexcitatory activities of Isocarboxazid.
TranylcypromineTranylcypromine may increase the orthostatic hypotensive activities of Isocarboxazid.
TrazodoneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Trazodone.
TrichlormethiazideThe serum concentration of Trichlormethiazide can be increased when it is combined with Isocarboxazid.
TrifluoperazineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Trifluoperazine.
TriflupromazineThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Triflupromazine.
UmeclidiniumUmeclidinium may increase the anticholinergic activities of Isocarboxazid.
VenlafaxineIsocarboxazid may increase the serotonergic activities of Venlafaxine.
ZiprasidoneThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Ziprasidone.
ZuclopenthixolThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Zuclopenthixol.
Food Interactions
  • Take without regard to meals, avoid tyramine, caffeine and alcohol.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Serotonin binding
Specific Function:
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.
Gene Name:
MAOA
Uniprot ID:
P21397
Molecular Weight:
59681.27 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Thase ME, Trivedi MH, Rush AJ: MAOIs in the contemporary treatment of depression. Neuropsychopharmacology. 1995 May;12(3):185-219. [PubMed:7612154 ]
  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:2248058 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Primary amine oxidase activity
Specific Function:
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.
Gene Name:
MAOB
Uniprot ID:
P27338
Molecular Weight:
58762.475 Da
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:4070383 ]
  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:2248058 ]
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Drug created on June 13, 2005 07:24 / Updated on May 02, 2014 14:23