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Classical MAOIs, including isocarboxazid, are used only very rarely in the present day due to prominent ] and ]s and have been largely superseded by newer, safer, and more tolerable antidepressants such as the ]s (SSRIs). The cause of the interactions is due to the fact that MAOIs inhibit the ] of dietary amines (e.g., ]) 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 ]s, MAOIs can produce dangerous elevations of monoamine neurotransmitters resulting in potentially life-threatening syndromes such as ] and ]. Classical MAOIs, including isocarboxazid, are used only very rarely in the present day due to prominent ] and ]s and have been largely superseded by newer, safer, and more tolerable antidepressants such as the ]s (SSRIs). The cause of the interactions is due to the fact that MAOIs inhibit the ] of dietary amines (e.g., ]) 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 ]s, MAOIs can produce dangerous elevations of monoamine neurotransmitters resulting in potentially life-threatening syndromes such as ] and ].
==Chemistry==

], the hydrazide of pyridine-4-carboxylic acid, is still, well over half a century after its discovery, one of the mainstays for the treatment of ]. Widespread use led to the serendipitous discovery of its antidepressant activity. This latter activity is retained when ] is replaced by ].
==Synthesis==
] (not ]) is the starting material, which on ] with ] gives 5-methyl-isoxazol-3-carboxylic acid
] (1959).]]
== See also == == See also ==
* ] * ]

Revision as of 13:30, 9 January 2015

Pharmaceutical compound
Isocarboxazid
Clinical data
Trade namesMarplan
AHFS/Drugs.comConsumer Drug Information
MedlinePlusa605036
Pregnancy
category
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: WARNING
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability?
MetabolismLiver
Elimination half-life?
ExcretionUrine
Identifiers
IUPAC name
  • N′-benzyl-5-methylisoxazole-3-carbohydrazide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.399 Edit this at Wikidata
Chemical and physical data
FormulaC12H13N3O2
Molar mass231.25 g·mol
3D model (JSmol)
SMILES
  • O=C(NNCc1ccccc1)c2noc(c2)C
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)
  • Key:XKFPYPQQHFEXRZ-UHFFFAOYSA-N
  (what is this?)  (verify)

Isocarboxazid (Marplan, Marplon, Enerzer) is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class used as an antidepressant. 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, though it is not as commonly employed in comparison to the others.

Isocarboxazid is primarily used to treat mood and anxiety disorders. It has also been investigated in the treatment of Parkinson's disease and other dementia-related disorders. Although efficacious, isocarboxazid produces many side effects, which may include headaches, jaundice, chest pain, weight gain, orthostatic hypotension, fainting, dizziness, and tremors. Isocarboxazid, as well as other MAOIs, increase the levels of the monoamine neurotransmitters serotonin, dopamine, and norepinephrine in the brain.

Classical MAOIs, including isocarboxazid, are used only very rarely in the present day due to prominent food and drug interactions and have been largely superseded by newer, safer, and more tolerable antidepressants such as the selective serotonin reuptake inhibitors (SSRIs). The cause of the interactions is due to the fact that 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.

Chemistry

Isoniazide, the hydrazide of pyridine-4-carboxylic acid, is still, well over half a century after its discovery, one of the mainstays for the treatment of tuberculosis. Widespread use led to the serendipitous discovery of its antidepressant activity. This latter activity is retained when pyridine is replaced by isoxazole.

Synthesis

Acetonylacetone (not Acetylacetone) is the starting material, which on nitrosation with nitrous acid gives 5-methyl-isoxazol-3-carboxylic acid

Isocarboxazid synthesis: U.S. patent 2,908,688 Hoffmann La Roche (1959).

See also

References

  1. "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.
  2. Fagervall I, Ross SB (April 1986). "Inhibition of monoamine oxidase in monoaminergic neurones in the rat brain by irreversible inhibitors". Biochemical pharmacology. 35 (8): 1381–7. doi:10.1016/0006-2952(86)90285-6. PMID 2870717.
  3. ^ David Rosenberg (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.
  4. ^ Lawrence A. Labbate; Maurizio Fava; Jerrold F. Rosenbaum (28 March 2012). Handbook of Psychiatric Drug Therapy. Lippincott Williams & Wilkins. pp. 99–. ISBN 978-1-4511-5307-1. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  5. Volz, Hanz-Peter. (November 1998) “Monoamine Oxidase Inhibitors A Perspective on Their Use in The Elderly” Biochemical pharmacology (5) 341-352.
  6. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1021/jm50009a002, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1021/jm50009a002 instead.


Antidepressants (N06A)
Specific reuptake inhibitors and/or receptor modulators
SSRIsTooltip Selective serotonin reuptake inhibitors
SNRIsTooltip Serotonin–norepinephrine reuptake inhibitors
NRIsTooltip Norepinephrine reuptake inhibitors
NDRIsTooltip Norepinephrine–dopamine reuptake inhibitors
NaSSAsTooltip Noradrenergic and specific serotonergic antidepressants
SARIsTooltip Serotonin antagonist and reuptake inhibitors
SMSTooltip Serotonin modulator and stimulators
Others
Tricyclic and tetracyclic antidepressants
TCAsTooltip Tricyclic antidepressants
TeCAsTooltip Tetracyclic antidepressants
Others
Monoamine oxidase inhibitors
Non-selective
MAOATooltip Monoamine oxidase A-selective
MAOBTooltip Monoamine oxidase B-selective
Adjunctive therapies
Miscellaneous

Template:Monoaminergics

Hydrazines


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