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].

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.

Absorption, Distribution and Excretion
The pharmacokinetic profile of isocarboxazid have not been fully studied but it is suggested that its properties should be fairly similar to the ones of some analogs like phenelzine and tranylcypromine. These drugs are readily absorbed by the GI tract, present a low bioavailability and reach peak concentrations in 1-2 hours.
Most of the eliminated dose is found in the urine, accounting for the 42.5% of the administered dose after 24 hours. From this amount, 75% of the renally eliminated drug is in the form of hippuric acid. Another section of the eliminated dose is observed through the intestinal tract and it accounts for 22% of the administered dose after 24 hours.

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Metabolism / Metabolites
The pharmacokinetic profile of isocarboxazid have not been fully studied but it is suggested that its properties should be fairly similar to the ones of some analogs like phenelzine and tranylcypromine. These drugs are rapidly metabolized by acetylation in the liver. As part of the metabolism, hippuric acid is a major metabolite.
Hepatic and rapid (by oxidation).

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Biological Half-Life
The pharmacokinetic profile of isocarboxazid have not been fully studied but it is suggested that its properties should be fairly similar to the ones of some analogs like phenelzine and tranylcypromine. The isocarboxazid half-life is of little interest as it is an irreversible monoamine oxidase inhibitor. These drugs present a very short half-life of 1.5-4 hours due to rapid hepatic metabolism.

Toxicity Summary
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.

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Hepatotoxicity
Isocarboxazid, like most monoamine oxidase (MAO) inhibitors, can cause transient serum aminotransferase elevations in a proportion of patients. These elevations are usually mild, asymptomatic and self-limited and do not require dose modification. MAO inhibitors have been associated with rare cases of acute, clinically apparent liver injury but isocarboxazid has not specifically been implicated. The time to clinical onset of liver injury due to MAO inhibitors is typically 1 to 4 months after starting and the usual pattern of serum enzyme elevations is hepatocellular, although cholestatic injury has also been described. Immunoallergic features (rash, fever, eosinophilia) are uncommon as is autoantibody formation. Isocarboxazid has not been directly implicated in cases of drug-induced liver injury but it has had limited clinical use.
Likelihood score: E* (unproven, but suspected rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because of the lack of data on use during breastfeeding, other antidepressants are preferred during breastfeeding.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
The pharmacokinetic profile of isocarboxazid have not been fully studied but it is suggested that its properties should be fairly similar to the ones of some analogs like phenelzine and tranylcypromine. These drugs present a very high protein binding percentage.

[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-isoxazolecarbohydrazide is a member of benzenes.
Isocarboxazid has the formula 1-benzyl-2-(5-methyl-3-isoxazolylcarbonyl)hydrazine-isocarboxazid. It is a monoamine oxidase inhibitor. It is used in the treatment of major depression, dysthymic disorder, atypical disorder, panic disorder and the phobic disorders. It was first introduced by Roche pharmaceuticals, further developed by Validus pharms Inc and first FDA approved as a prescription drug on July 1st, 1959.
Isocarboxazid is a Monoamine Oxidase Inhibitor. The mechanism of action of isocarboxazid is as a Monoamine Oxidase Inhibitor.
Isocarboxazid is a monoamine oxidase inhibitor (MAO inhibitor) used in therapy of severe depression. Isocarboxazid therapy is associated with rare instances of clinically apparent acute liver injury.
Isocarboxazid is a hydralazine and monoamine oxidase (MAO) inhibitor with antidepressant activity. Isocarboxazid blocks the breakdown (oxidative deamination) of biogenic amines by inhibiting MAO, thereby increasing the concentrations of norepinephrine and 5-hydroxytrytamine (5-HT) at central aminergic receptors. These neurotransmitters are involved in sustaining mood and emotions. The down-regulation of central beta-adrenergic and serotonergic receptors by chronic inhibition of MAO may also contribute to the antidepressant effects seen by isocarboxazid. (NCI05)
Isocarboxazid is only found in individuals that have used or taken this drug. It is an MAO inhibitor that is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in the treatment of panic disorder and the phobic disorders. (From AMA, Drug Evaluations Annual, 1994, p311). 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.
An MAO inhibitor that is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in the treatment of panic disorder and the phobic disorders. (From AMA, Drug Evaluations Annual, 1994, p311)

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Drug Indication
Isocarboxazid is indicated for the treatment of the enduring and debilitating symptoms of depression that have not responded to other antidepressant drugs. Depression is a common but serious mood disorder. The patient will present changes in its feelings, thoughts, and ability to handle everyday activities. For a mood disorder to be considered as depression, the symptoms should be present for at least two weeks.
FDA Label

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Mechanism of Action
Isocarboxazid works by irreversibly blocking the action of monoamine oxidases (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). Isocarboxacid, like other monoamine oxidase inhibitors, are unique psychopharmacological agents whose clinical effect is related to the direct action of the monoamine oxidases to transform them into reactive metabolites.

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Pharmacodynamics
In vivo and in vitro studies demonstrated isocarboxazid-driven inhibition of MAO in the brain, heart, and liver. The reduced MAO activity, caused by isocarboxazid, results in an increased concentration of serotonin, epinephrine, norepinephrine, and dopamine in storage sites throughout the central nervous system (CNS) and sympathetic nervous system. The increase of one or more monoamines is the basis for the antidepressant activity of MAO inhibitors like isocarboxazid.

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.)