Isocarboxazid targets monoamine oxidase (MAO), an enzyme responsible for the oxidative deamination of biogenic amines. By inhibiting MAO, isocarboxazid blocks the breakdown of neurotransmitters such as norepinephrine and serotonin (5-HT), increasing their concentrations at central aminergic receptors. This leads to enhanced neurotransmission and antidepressant effects.

Isocarboxazid is a potent inhibitor of monoamine oxidase. Its in vitro activity is characterized by its ability to inhibit MAO activity in enzyme assays. By blocking the breakdown of biogenic amines, it increases the levels of these neurotransmitters in synaptic clefts. This mechanism is responsible for its antidepressant effects.

Isocarboxazid (1, 3 mg/kg, i.p., 60 min) intermittent clock indicated a substantial increase in the frequency of peak withdrawals at 15 and 30 min following 5-HTP [2]. Isocarboxazid (1,3 mg/kg, i.p., 60 minutes). , 60 minutes) treatment of mice with a 5-HTP catalyst resulted in a 43% increase in 5-HT concentrations and a 22% drop in 5-HIAA compared to the brains of mice given 5-HTP alone [2].
Isocarboxazid is effective in vivo for the treatment of major depression, dysthymic disorder, atypical depression, panic disorder, and phobic disorders. By inhibiting MAO, it increases the levels of norepinephrine and serotonin in the brain, leading to improved mood and reduced anxiety. Its clinical efficacy has been demonstrated in numerous studies since its introduction in 1959.

The primary in vitro assay for isocarboxazid is an enzyme activity assay using purified MAO. The enzyme is incubated with a substrate, such as serotonin or tyramine, and the production of the deaminated metabolite is measured in the presence of the compound. The IC50 value is determined from dose-response curves, indicating the compound's potency as an MAO inhibitor.

In vitro cellular assays for isocarboxazid involve treating neuronal cells with the compound and measuring the levels of neurotransmitters such as norepinephrine and serotonin. The compound's ability to increase neurotransmitter levels confirms its MAO inhibitory activity in a cellular context. These assays can also be used to study the effects of MAO inhibition on neuronal function.

Animal/Disease Models: 12 dd strain male mice (20-25 g) [2]
Doses: 0, 0.3, 1, 3 mg/kg
Route of Administration: intraperitoneal (ip) injection 60 minutes before intravenous (iv) (iv)injection of 5-HTP
Experimental Results: 15 times and 15 head twitches increased 5-HTP 30 minutes later. There was a 43% increase in 5-HT concentration and a 22% decrease in 5-HIAA concentration.
In vivo animal experiments for isocarboxazid involve administering the compound to animal models of depression, such as the forced swim test or tail suspension test in rodents. The compound's ability to reduce immobility time in these tests indicates its antidepressant efficacy. Its effects on neurotransmitter levels in the brain can also be measured.

Absorption, Distribution and Excretion
The pharmacokinetic characteristics of isocarboxazid have not been fully studied, but it is presumed that its properties are comparable to some analogues such as phenelzine and transphenylcyclopropane. These drugs are readily absorbed from the gastrointestinal tract, have low bioavailability, and reach peak plasma concentrations within 1–2 hours. Most of the drug is excreted in the urine, with approximately 42.5% of the administered dose remaining after 24 hours. Of this, 75% is excreted by the kidneys as hippuric acid. Another portion of the eliminated dose is excreted through the intestines, with approximately 22% of the administered dose remaining after 24 hours. Metabolism/Metabolites The pharmacokinetic characteristics of isocarboxazid have not been fully studied, but it is presumed that its properties are comparable to some analogues such as phenelzine and transphenylcyclopropane. These drugs are rapidly metabolized in the liver via acetylation. Hippuric acid is one of the major metabolites. Hepatic metabolism is rapid (through oxidation).

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Biological Half-Life
The pharmacokinetic characteristics of isocarboxazid have not been fully studied, but it is speculated that its properties are comparable to some analogues such as phenelzine and transphenylcyclopropane. Since isocarboxazid is an irreversible monoamine oxidase inhibitor, its half-life is of little significance. Due to rapid hepatic metabolism, these drugs have very short half-lives, only 1.5-4 hours.

Isocarboxazid has a molecular weight of 231.25 and a molecular formula of C12H13N3O2. It is orally administered and is absorbed from the gastrointestinal tract. The compound is metabolized in the liver, and its pharmacokinetic properties, such as half-life and bioavailability, have been characterized. It is a hydrazine derivative, and its metabolism may involve acetylation or other pathways.

Toxicity Summary
Iscarbazid works by irreversibly blocking the activity of a chemical in the nervous system called monoamine oxidase (MAO). MAO A and B subtypes are involved in the metabolism of serotonin and catecholamine neurotransmitters such as adrenaline, noradrenaline, and dopamine. As a non-selective MAO inhibitor, iscarbazid irreversibly binds to both MAO-A and MAO-B. Reduced MAO activity leads to increased concentrations of these neurotransmitters at their storage sites in the central nervous system (CNS) and sympathetic nervous system. The antidepressant activity of monoamine oxidase inhibitors (MAO inhibitors) is based on increasing the availability of one or more monoamines.
Hepatotoxicity
Like most monoamine oxidase inhibitors, iscarbazid can cause transient increases in serum transaminases in some patients. These increases are usually mild, asymptomatic, and resolve spontaneously without dose adjustment. MAO inhibitors are associated with rare cases of acute, clinically significant liver injury, but a direct association between isocarboxazid and such injury has not been found. MAO inhibitor-induced liver injury typically presents with clinical symptoms 1 to 4 months after initiation of treatment. The common pattern of elevated serum enzymes is hepatocellular, but cholestatic liver injury has also been reported. Immune allergic reactions (rash, fever, eosinophilia) and autoantibody formation are uncommon. Isocarboxazid has not been directly confirmed to be associated with drug-induced liver injury, and its clinical use is limited. Probability score: E (Unconfirmed, but suspected as a rare cause of clinically significant liver injury). Effects during pregnancy and lactation: ◉ Overview of medication use during lactation: Due to a lack of data on medication use during lactation, other antidepressants should be preferred during lactation. ◉ Effects on breastfed infants: As of the revision date, no relevant published information was found.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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Protein binding
The pharmacokinetic characteristics of isocarboxazid have not been fully studied, but it is speculated that its properties should be comparable to some analogues such as phenelzine. Trans-cyclopropylamine. These drugs have very high protein binding rates.
The toxicological profile of isocarboxazid is characteristic of MAOIs. Common adverse effects include orthostatic hypotension, dizziness, drowsiness, and weight gain. MAOIs can also cause hypertensive crisis when combined with tyramine-rich foods or certain medications. Isocarboxazid is contraindicated in patients with liver disease, pheochromocytoma, and those taking other MAOIs or serotonergic drugs.

[1]. Relative activity of some inhibitors of mono-amine oxidase in potentiating the action of tryptamine in vitro and in vivo. Br J Pharmacol Chemother. 1961 Dec;17:310-20.

5-Methyl-N'-(phenylmethyl)-3-isoxazolylhydrazide belongs to the benzene family of compounds. The molecular formula of isocarboxazide is 1-benzyl-2-(5-methyl-3-isoxazolylcarbonyl)hydrazine-isocarboxazide. It is a monoamine oxidase inhibitor. It is used to treat major depressive disorder, dysthymia, atypical disorder, panic disorder, and phobias. It was initially introduced by Roche Pharmaceuticals, further developed by Validus Pharmaceuticals, and first approved as a prescription drug by the U.S. Food and Drug Administration (FDA) on July 1, 1959. Isocarboxazide is a monoamine oxidase inhibitor. Its mechanism of action is as a monoamine oxidase inhibitor. Isocarboxazide is a monoamine oxidase inhibitor (MAO inhibitor) used to treat major depressive disorder. Isocarboxazide treatment has been associated with rare cases of clinically significant acute liver injury. Isocarboxazide is a hydralazine derivative and a monoamine oxidase (MAO) inhibitor with antidepressant activity. Iscarbazide works by inhibiting monoamine oxidase (MAO), which blocks the breakdown of biogenic amines (oxidative deamination), thereby increasing the concentration of norepinephrine and serotonin (5-HT) at central aminoagent receptors. These neurotransmitters are involved in maintaining mood and affect. Long-term MAO inhibition leads to downregulation of central β-adrenergic and serotonergic receptors, which may be one of the reasons why iscarbazide exerts its antidepressant effect. (NCI05)
Iscarbazide has only been found in individuals who have used or taken the drug. It is an MAO inhibitor that is effective in treating major depressive disorder, dysthymia, and atypical depression. It is also used to treat panic disorder and phobias. (Adapted from JAMA, Annals of Drug Evaluation, 1994, p. 311). The mechanism of action of iscarbazide is the irreversible blocking of the activity of a chemical in the nervous system called monoamine oxidase (MAO). MAO A and B subtypes are involved in the metabolism of serotonin and catecholamine neurotransmitters such as adrenaline, noradrenaline, and dopamine. Iscarbazi, a non-selective MAO inhibitor, irreversibly binds to monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). Decreased MAO activity leads to increased concentrations of these neurotransmitters at their storage sites in the central nervous system (CNS) and sympathetic nervous system. The antidepressant activity of monoamine oxidase inhibitors (MAO inhibitors) is based on increased availability of one or more monoamines. MAO inhibitors are effective in treating major depressive disorder, dysthymia, and atypical depression. They are also used to treat panic disorder and phobias. (Adapted from JAMA, Annals of Drug Evaluation, 1994, p. 311) Drug Indications Iscarbazi is indicated for the treatment of persistent, disabling depressive symptoms unresponsive to other antidepressants. Depression is a common but serious mental disorder. Patients experience changes in mood, thinking, and the ability to perform daily activities. Symptoms must persist for at least two weeks to be diagnosed with depression.
FDA Label

Mechanism of Action

Iscarbazid works by irreversibly blocking the activity of monoamine oxidase (MAO) in the nervous system. Monoamine oxidase (MAO) types A and B are involved in the metabolism of serotonin and catecholamine neurotransmitters such as adrenaline, noradrenaline, and dopamine. Iscarbazid, as a non-selective MAO inhibitor, irreversibly binds to both MAO-A and MAO-B. Like other MAO inhibitors, iscarbazid is a unique psychopharmacological drug whose clinical efficacy is related to the direct action of MAO on monoamines, converting them into active metabolites.
Pharmacodynamics

In vivo and in vitro studies have shown that iscarbazid inhibits MAO activity in the brain, heart, and liver.
Iscarbazid-induced decrease in monoamine oxidase (MAO) activity leads to increased concentrations of serotonin, adrenaline, noradrenaline, and dopamine in storage sites within the central nervous system (CNS) and sympathetic nervous system. This increase in one or more monoamine neurotransmitters is the basis for the antidepressant effects of MAO inhibitors such as iscarbazid.
Isocarboxazid is a monoamine oxidase inhibitor used for the treatment of depression and other psychiatric disorders. It was introduced in 1959 and is marketed under the brand name Marplan. The compound is effective in treating major depression, dysthymic disorder, atypical depression, panic disorder, and phobic disorders. As an MAOI, it increases the levels of norepinephrine and serotonin in the brain by inhibiting their breakdown. It is available by prescription for the treatment of depression.

C12H13N3O2

231.25052

231.1

59-63-2

24631-64-9 (sulfate);59-63-2;

3759

White to off-white solid powder

1.2±0.1 g/cm3

394.5±42.0 °C at 760 mmHg

98-100ºC

192.4±27.9 °C

0.0±0.9 mmHg at 25°C

1.573

1.03

2

4

4

17

254

0

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)

N'-benzyl-5-methyl-1,2-oxazole-3-carbohydrazide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~432.43 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (10.81 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (10.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)