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 |
|---|---|---|---|---|
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 |
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 |
| 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 |
| 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 |
| 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 |
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 |
|---|---|---|
| Synthesis of novel N-substituted imidazolecarboxylic acid hydrazides as monoamine oxidase inhibitors. | 2005-03 |
|
| Toxic interaction of venlafaxine and isocarboxazide. | 1995-11-11 |
|
| Serotonin syndrome. | 1995-02 |
|
| Sertraline and isocarboxazid cause a serotonin syndrome. | 1994-04 |
|
| A trial of isocarboxazid in the treatment of bulimia nervosa. | 1988-12 |
|
| Mania induced by tricyclic-MAOI combination therapy in bipolar treatment-resistant disorder: case reports. | 1986-01 |
|
| Mania after withdrawal of isocarboxazid. | 1985-12 |
|
| The importance of dose in isocarboxazid therapy. | 1984-07 |
|
| Side effects of isocarboxazid. | 1984-07 |
|
| Acute lithium-induced tremor. | 1983-07 |
|
| Treatment of lithium-induced tremor and familial essential tremor with essential fatty acids. | 1981 |
|
| Linoleic acid in the treatment of lithium toxicity and familial tremor. | 1980-04 |
|
| Tricyclic antidepressants and monoamine oxidase inhibitors. | 1971-06 |
|
| Use of isocarboxazid in hypertensive patients. | 1966-07-01 |
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
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34237V843T
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N06AF01
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N0000000184
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N0000175744
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NBK548518
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QN06AF01
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C667
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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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100000082827
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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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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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ACTIVE MOIETY |