Isocarboxazid

Last updated
Isocarboxazid
Isocarboxazid structure.svg
Clinical data
Trade names Marplan
AHFS/Drugs.com Consumer Drug Information
MedlinePlus a605036
Pregnancy
category
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability Low, peak at 1-2 h [1]
Metabolism Liver (Carboxylesterase [2] )
Metabolites Hippuric acid [3]
Elimination half-life 1.5-4h [1]
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 (Marplan, Marplon, Enerzer) is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class used as an antidepressant. [4] 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, [5] [6] though it is not as commonly employed in comparison to the others. [5] [6]

Isocarboxazid is primarily used to treat mood and anxiety disorders. It has also been investigated in the treatment of schizophrenia, [7] Parkinson's disease and other dementia-related disorders. [8]

Isocarboxazid, as well as other MAOIs, increase the levels of the monoamine neurotransmitters serotonin, dopamine, norepinephrine, epinephrine, melatonin, phenethylamine in the brain. [9]

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MAOIs, including isocarboxazid, are used only rarely due to prominent food and drug interactions and have been largely superseded by newer antidepressants such as the selective serotonin reuptake inhibitors (SSRIs).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.

See also

Related Research Articles

<span class="mw-page-title-main">Antidepressant</span> Class of medication used to treat depression and other conditions

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.

<span class="mw-page-title-main">Psychiatric medication</span> Medication used to treat mental disorders

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

Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin.

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

Phenelzine, sold under the brand name Nardil, among others, is a non-selective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class which is primarily used as an antidepressant and anxiolytic. Along with tranylcypromine and isocarboxazid, phenelzine is one of the few non-selective and irreversible MAOIs still in widespread clinical use. It is typically available in 15 mg tablets and doses usually range from 45–90 mg per day.

<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.

<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, obsessive–compulsive disorder (OCD), social phobia, attention-deficit hyperactivity disorder (ADHD), chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. 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), which act upon serotonin only.

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

Moclobemide, sold under the brand names Amira, Aurorix, Clobemix, Depnil and Manerix among others, is a reversible inhibitor of monoamine oxidase A (RIMA) drug primarily used to treat depression and social anxiety. It is not approved for use in the United States, but is approved in other Western countries such as Canada, the UK and Australia. It is produced by affiliates of the Hoffmann–La Roche pharmaceutical company. Initially, Aurorix was also marketed by Roche in South Africa, but was withdrawn after its patent rights expired and Cipla Medpro's Depnil and Pharma Dynamic's Clorix became available at half the cost.

Antidepressant discontinuation syndrome, also called antidepressant withdrawal syndrome, is a condition that can occur following the interruption, reduction, or discontinuation of antidepressant medication following its continuous use of at least a month. The symptoms may include flu-like symptoms, trouble sleeping, nausea, poor balance, sensory changes, akathesia, intrusive thoughts, depersonalization and derealization, mania, anxiety, and depression. The problem usually begins within three days and may last for several months or years. Rarely psychosis may occur.

<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.

Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include: alter intrinsic firing activity, increase or decrease voltage-dependent currents, alter synaptic efficacy, increase bursting activity and reconfiguration of synaptic connectivity.

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

Rasagiline is an irreversible inhibitor of monoamine oxidase-B used as a monotherapy to treat symptoms in early Parkinson's disease or as an adjunct therapy in more advanced cases.

A serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), also known as a triple reuptake inhibitor (TRI), is a type of drug that acts as a combined reuptake inhibitor of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine. It does this by concomitantly inhibiting the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT), respectively. Inhibition of the reuptake of these neurotransmitters increases their extracellular concentrations and, therefore, results in an increase in serotonergic, adrenergic, and dopaminergic neurotransmission. The naturally-occurring and potent SNDRI cocaine is widely used recreationally and often illegally for the euphoric effects it produces.

<span class="mw-page-title-main">Reuptake inhibitor</span> Type of drug

A reuptake inhibitor (RI) is a type of drug known as a reuptake modulator that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron. This leads to an increase in extracellular concentrations of the neurotransmitter and an increase in neurotransmission. Various drugs exert their psychological and physiological effects through reuptake inhibition, including many antidepressants and psychostimulants.

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

The hydrazine antidepressants are a group of non-selective, irreversible monoamine oxidase inhibitors (MAOIs) which were discovered and initially marketed in the 1950s and 1960s. Most have been withdrawn due to toxicity, namely hepatotoxicity, but a few still remain in clinical use.

The psychopharmacology revolution covers the introduction of various psychiatric drugs into clinical practice as well as their continued development. Although not exclusively limited to the 1950s period, the literature tends to suggest that this decade was a particularly fruitful time for CNS drug discovery and it has been referred to as a "golden era".

Selective serotonin reuptake inhibitors, or serotonin-specific re-uptake inhibitor (SSRIs), are a class of chemical compounds that have contributed to the major advances as antidepressants where they have revolutionised the treatment of depression and other psychiatric disorders. The SSRIs are therapeutically useful in the treatment of panic disorder (PD), posttraumatic stress disorder (PTSD), social anxiety disorder, obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder (PMDD), and anorexia. There is also clinical evidence of SSRIs efficiency in the treatment of the negative symptoms of schizophrenia and their ability to prevent cardiovascular diseases.

Antidepressant treatment tachyphylaxis, also known as Prozac poop-out, is a medical condition in which progressive or acute tolerance effects are seen following chronic administration of a drug. It occurs more often with Selective serotonin reuptake inhibitors (SSRIs), which are the most commonly prescribed antidepressants.

References

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  2. 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.
  3. "Reaction: Isocarboxazid to 1 product". go.drugbank.com. Retrieved 27 October 2021.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Riederer P, Laux G (March 2011). "MAO-inhibitors in Parkinson's Disease". Experimental Neurobiology. Experimental Neurology. 20 (1): 1–17. doi:10.5607/en.2011.20.1.1. PMC   3213739 . PMID   22110357.
  9. 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.