Details
Stereochemistry | ACHIRAL |
Molecular Formula | C12H13N3O2 |
Molecular Weight | 231.2505 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=CC(=NO1)C(=O)NNCC2=CC=CC=C2
InChI
InChIKey=XKFPYPQQHFEXRZ-UHFFFAOYSA-N
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)
Molecular Formula | C12H13N3O2 |
Molecular Weight | 231.2505 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: http://www.drugbank.ca/drugs/DB01247Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/mtm/marplan.html
Sources: http://www.drugbank.ca/drugs/DB01247
Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/mtm/marplan.html
Isocarboxazid (Marplan, Marplon, Enerzer) is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class used as an antidepressant. 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. 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. May be used to treat major depressive disorder.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3217380 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22535688 |
128.0 nM [IC50] | ||
Target ID: CHEMBL2095205 Sources: http://www.genome.jp/dbget-bin/www_bget?D02580 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Sources: https://www.drugs.com/pro/marplan.html |
Primary | Marplan Approved UseMarplan is indicated for the treatment of depression. Because of its potentially serious side effects, Marplan is not an antidepressant of first choice in the treatment of newly diagnosed depressed patients. Launch Date1959 |
Doses
Dose | Population | Adverse events |
---|---|---|
80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: |
unhealthy, 18 - 65 years n = 3 Health Status: unhealthy Condition: depression Age Group: 18 - 65 years Population Size: 3 Sources: |
Disc. AE: Hyperreflexia, Hyperexcitability... AEs leading to discontinuation/dose reduction: Hyperreflexia (1 patient) Sources: Hyperexcitability (1 patient) Agitation (1 patient) Weakness (1 patient) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Agitation | 1 patient Disc. AE |
80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: |
unhealthy, 18 - 65 years n = 3 Health Status: unhealthy Condition: depression Age Group: 18 - 65 years Population Size: 3 Sources: |
Hyperexcitability | 1 patient Disc. AE |
80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: |
unhealthy, 18 - 65 years n = 3 Health Status: unhealthy Condition: depression Age Group: 18 - 65 years Population Size: 3 Sources: |
Hyperreflexia | 1 patient Disc. AE |
80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: |
unhealthy, 18 - 65 years n = 3 Health Status: unhealthy Condition: depression Age Group: 18 - 65 years Population Size: 3 Sources: |
Weakness | 1 patient Disc. AE |
80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: |
unhealthy, 18 - 65 years n = 3 Health Status: unhealthy Condition: depression Age Group: 18 - 65 years Population Size: 3 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 61.0 |
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://europepmc.org/article/med/26692222 Page: abstract |
no |
PubMed
Title | Date | PubMed |
---|---|---|
Use of isocarboxazid in hypertensive patients. | 1966 Jul-Aug |
|
Tricyclic antidepressants and monoamine oxidase inhibitors. | 1971 Jun |
|
Linoleic acid in the treatment of lithium toxicity and familial tremor. | 1980 Apr |
|
Treatment of lithium-induced tremor and familial essential tremor with essential fatty acids. | 1981 |
|
Acute lithium-induced tremor. | 1983 Jul |
|
The importance of dose in isocarboxazid therapy. | 1984 Jul |
|
Side effects of isocarboxazid. | 1984 Jul |
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Mania after withdrawal of isocarboxazid. | 1985 Dec |
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Mania induced by tricyclic-MAOI combination therapy in bipolar treatment-resistant disorder: case reports. | 1986 Jan |
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A trial of isocarboxazid in the treatment of bulimia nervosa. | 1988 Dec |
|
Sertraline and isocarboxazid cause a serotonin syndrome. | 1994 Apr |
|
Serotonin syndrome. | 1995 Feb |
|
Toxic interaction of venlafaxine and isocarboxazide. | 1995 Nov 11 |
|
Synthesis of novel N-substituted imidazolecarboxylic acid hydrazides as monoamine oxidase inhibitors. | 2005 Mar |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/marplan.html
Dosage should be started with one tablet (10 mg) of Marplan (Isocarboxazid) twice daily. If tolerated, dosage may be increased by increments of one tablet (10 mg) every 2 to 4 days to achieve a dosage of four tablets daily (40 mg) by the end of the first week of treatment. Dosage can then be increased by increments of up to 20 mg/week, if needed and tolerated, to a maximum recommended dosage of 60 mg/day. Daily dosage should be divided into two to four dosages.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2248058
Unknown
Substance Class |
Chemical
Created
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admin
on
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Record UNII |
34237V843T
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Record Status |
Validated (UNII)
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Record Version |
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WHO-ATC |
N06AF01
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NDF-RT |
N0000000184
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N0000175744
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LIVERTOX |
NBK548518
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WHO-VATC |
QN06AF01
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NCI_THESAURUS |
C667
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NCI_THESAURUS |
C265
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D007520
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DB01247
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6011
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m6472
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169893
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7204
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C47573
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CHEMBL1201168
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1071
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34237V843T
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59-63-2
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ISOCARBOXAZID
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SUB08313MIG
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DTXSID4023171
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34237V843T
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Isocarboxazid
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3759
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200-438-4
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