Isocarboxazid

Last updated
Isocarboxazid
Isocarboxazid structure.svg
Clinical data
Trade names Marplan, Enerzer
AHFS/Drugs.com Consumer Drug Information
MedlinePlus a605036
Pregnancy
category
  • C (US)
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • BR: Class C1 (Other controlled substances) [1]
  • US: WARNING [2]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability Low, peak at 1–2 h [3]
Metabolism Liver (Carboxylesterase [4] )
Metabolites Hippuric acid [5]
Elimination half-life 1.5–4 h [3]
Excretion Urine
Identifiers
  • N′-benzyl-5-methylisoxazole-3-carbohydrazide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.399 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C12H13N3O2
Molar mass 231.255 g·mol−1
3D model (JSmol)
  • O=C(NNCc1ccccc1)c2noc(c2)C
  • 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) Yes check.svgY
  • Key:XKFPYPQQHFEXRZ-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Isocarboxazid, sold under the brand name Marplan among others, is a non-selective irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class used as an antidepressant. [6] Along with phenelzine and tranylcypromine, it is one of only three classical MAOIs still available for clinical use in the treatment of psychiatric disorders in the United States, [7] [8] though it is not as commonly employed in comparison to the others. [7] [8]

Contents

Isocarboxazid is primarily used to treat mood and anxiety disorders. It has also been investigated in the treatment of schizophrenia, [9] Parkinson's disease, and other dementia-related disorders. [10]

Isocarboxazid, as well as other MAOIs, increase the levels of the monoamine neurotransmitters serotonin, dopamine, norepinephrine, epinephrine, melatonin, and phenethylamine in the brain. [11]

Classical MAOIs, including isocarboxazid, are used only rarely due to prominent food and drug interactions and have been largely superseded by newer antidepressants such as the selective serotonin reuptake inhibitors (SSRIs). The cause of the interactions is because MAOIs inhibit the metabolism of dietary amines (e.g., tyramine) and the monoamine neurotransmitters. In combination with other drugs that increase the levels of the monoamine neurotransmitters such as the SSRIs, or with certain foods high in dietary amines such as aged cheeses, MAOIs can produce dangerous elevations of monoamine neurotransmitters resulting in potentially life-threatening syndromes such as hypertensive crisis and serotonin syndrome.

Contraindications

Isocarboxazid is contraindicated [12] [13] in certain patient populations, in combination with certain other drugs, and in combination with certain foods due to the risk of serious adverse reactions. Some notable contraindications include:

See also

Related Research Articles

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Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction.

An anxiolytic is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiety disorders and their related psychological and physical symptoms.

<span class="mw-page-title-main">Monoamine oxidase inhibitor</span> Type of medication

Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especially for treatment-resistant depression and atypical depression. They are also used to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders.

<span class="mw-page-title-main">Monoamine oxidase</span> Family of enzymes

Monoamine oxidases (MAO) are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first such enzyme was discovered in 1928 by Mary Bernheim in the liver and was named tyramine oxidase. The MAOs belong to the protein family of flavin-containing amine oxidoreductases.

A psychiatric or psychotropic medication is a psychoactive drug taken to exert an effect on the chemical makeup of the brain and nervous system. Thus, these medications are used to treat mental illnesses. These medications are typically made of synthetic chemical compounds and are usually prescribed in psychiatric settings, potentially involuntarily during commitment. Since the mid-20th century, such medications have been leading treatments for a broad range of mental disorders and have decreased the need for long-term hospitalization, thereby lowering the cost of mental health care. The recidivism or rehospitalization of the mentally ill is at a high rate in many countries, and the reasons for the relapses are under research.

<span class="mw-page-title-main">Monoamine neurotransmitter</span> Monoamine that acts as a neurotransmitter or neuromodulator

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<span class="mw-page-title-main">Phenelzine</span> Irreversible non-selective Monoamine Oxidase Inhibitor Antidepressant

Phenelzine, sold under the brand name Nardil among others, is a non-selective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine family which is primarily used as an antidepressant and anxiolytic to treat depression and anxiety. Along with tranylcypromine and isocarboxazid, phenelzine is one of the few non-selective and irreversible MAOIs still in widespread clinical use.

<span class="mw-page-title-main">Tranylcypromine</span> Irreversible non-selective MAO inhibitor Antidepressant drug

Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively. It is also effective in the treatment of ADHD.

<span class="mw-page-title-main">Tyramine</span> Chemical compound

Tyramine, also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood-brain barrier, resulting in only non-psychoactive peripheral sympathomimetic effects following ingestion. A hypertensive crisis can result, however, from ingestion of tyramine-rich foods in conjunction with the use of monoamine oxidase inhibitors (MAOIs).

<span class="mw-page-title-main">Serotonin–norepinephrine reuptake inhibitor</span> Class of antidepressant medication

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, social phobia, chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. Off-label uses include treatments for attention-deficit hyperactivity disorder (ADHD), and obsessive–compulsive disorder (OCD). SNRIs are monoamine reuptake inhibitors; specifically, they inhibit the reuptake of serotonin and norepinephrine. These neurotransmitters are thought to play an important role in mood regulation. SNRIs can be contrasted with the selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which act upon single neurotransmitters.

<span class="mw-page-title-main">Selegiline</span> Irreversible Type-B selective Monoamine Oxidase Inhibitor

Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl, Zelapar, and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It has also been studied and used off-label for a variety of other indications, but has not been formally approved for any other use. The medication, in the form licensed for depression, has modest effectiveness for this condition that is similar to that of other antidepressants. Selegiline is provided as a swallowed tablet or capsule or an orally disintegrating tablet (ODT) for Parkinson's disease and as a patch applied to skin for depression.

<span class="mw-page-title-main">Moclobemide</span> Antidepressant

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<span class="mw-page-title-main">Nialamide</span> Antidepressant

Nialamide is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class that was used as an antidepressant. It was withdrawn by Pfizer several decades ago due to the risk of hepatotoxicity.

<span class="mw-page-title-main">Iproniazid</span> Antidepressant

Iproniazid is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class. It is a xenobiotic that was originally designed to treat tuberculosis, but was later most prominently used as an antidepressant drug. However, it was withdrawn from the market because of its hepatotoxicity. The medical use of iproniazid was discontinued in most of the world in the 1960s, but remained in use in France until its discontinuation in 2015.

<span class="mw-page-title-main">Rasagiline</span> Chemical compound

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<span class="mw-page-title-main">Iproclozide</span> Chemical compound

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<span class="mw-page-title-main">Pargyline</span> Chemical compound

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<span class="mw-page-title-main">Pheniprazine</span> Chemical compound

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<span class="mw-page-title-main">Hydrazine (antidepressant)</span> Group of antidepressants

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References

  1. ↑ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 Oct 2023.
  3. 1 2 Owens DC, Johnstone EC, Lawrie SM (January 2010). "Clinical psychopharmacology.". Companion to psychiatric studies. pp. 227–294. doi:10.1016/B978-0-7020-3137-3.00011-5. ISBN   9780702031373.
  4. ↑ Moroi K, Kuga T (April 1982). "Inhibitory effect of leptophos on carboxylesterase (isocarboxazid amidase) in rat liver". Toxicology Letters. 11 (1–2): 81–85. doi:10.1016/0378-4274(82)90110-2. PMID   6178187.
  5. ↑ "Reaction: Isocarboxazid to 1 product". go.drugbank.com. Retrieved 27 October 2021.
  6. ↑ Fagervall I, Ross SB (April 1986). "Inhibition of monoamine oxidase in monoaminergic neurones in the rat brain by irreversible inhibitors". Biochemical Pharmacology. 35 (8): 1381–1387. doi:10.1016/0006-2952(86)90285-6. PMID   2870717.
  7. 1 2 Rosenberg D (21 August 2013). Pocket Guide For The Textbook Of Pharmacotherapy For Child And Adolescent Psychiatric Disorders. Routledge. pp. 176–. ISBN   978-1-134-86002-9.
  8. 1 2 Labbate LA, Fava M, Rosenbaum JF, Arana GW (28 March 2012). Handbook of Psychiatric Drug Therapy. Lippincott Williams & Wilkins. pp. 99–. ISBN   978-1-4511-5307-1.
  9. ↑ Darling HF (October 1959). "Isocarboxazid (marplan) in ambulatory psychiatric patients". The American Journal of Psychiatry. 116 (4): 355–356. doi:10.1176/ajp.116.4.355. PMID   13814129.
  10. ↑ Riederer P, Laux G (March 2011). "MAO-inhibitors in Parkinson's Disease". Experimental Neurobiology. 20 (1). Experimental Neurology: 1–17. doi:10.5607/en.2011.20.1.1. PMC   3213739 . PMID   22110357.
  11. ↑ Volz HP, Gleiter CH (November 1998). "Monoamine oxidase inhibitors. A perspective on their use in the elderly". Drugs & Aging. 13 (5): 341–55. doi:10.2165/00002512-199813050-00002. PMID   9829163. S2CID   71158339.
  12. ↑ "Marplan Drug Label". dailymed.nlm.nih.gov. Retrieved 2025-01-25.
  13. ↑ "Marplan® (isocarboxazid) | Safety Information". marplan.com. Retrieved 2025-01-25.
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