Isocarboxazide

Monoamine—Oxidase Inhibitors. In the mid-1950s, tuberculosis patients with depression being treated with iproniazid (42) were occasionally reported to become euphoric. This observation led to the discovery of irreversible monoamine—oxidase (MAO) inhibiting properties. Hydrazine and nonhydrazine-related MAO inhibitors were subsequentiy shown to be antidepressants (122). Three other clinically effective irreversible MAO inhibitors have been approved for treatment of major depression phenelzine (43), isocarboxazid (44), and tranylcypromine (45). 

Isobenzopyrylium salts, 1,3-diphenyl-synthesis, 3, 872 Isobutyropyrrothine biological activity, 6, 1024 Isocaffeine, 8-carboxymethyl-synthesis, S, 593 Isocarboxazid... 

Warfarin sodium Benzal acetophenone Alkofanone Benzaldehyde Butalamlne HCI Chloramphenicol Fenipentol Isocarboxazid Oxacillin sodium Penicillin G benzathine Phenylpropanolamine HCI Tripelennamine Benzaldehyde cyanohydrin Ethotoin... 

As early as 1961, the first generation of MAO inhibitors (iproniazid, isocarboxazide) were employed for the treatment of Parkinson s disease (PD). However, because of the severe side effects, such as cheese reaction, they were abandoned. The realization that the basal ganglia (extrapyramidal region) of human brain contained mostly MAO-B, which metabolized... 

Ethionamide Ethoheptazine Ethyl biscoumacetate Etiroxate Fenoxazoline Flurbiprofen Indobufen Indoramin Isocarboxazid Lofexidine Methotrexate Methyidopate Methylphenobarbital Nadoxolol Naphazoline Petindopril Phcnobarbital Propiverine Protionamide Proxazole Pyridoxine Retinol Thiamphenicol Tolazoline Tribenoside ethanolamine... 

With the exception of tranylcypromine (a phenylcycloalkylamine), the first MAOIs (e.g. iproniazid, isoniazid, phenelzine, isocarboxazid) were derivatives of hydrazine (originally used as a rocket fuel) (Fig. 20.2). All are irreversible inhibitors of the enzyme and restoration of MAO activity requires the synthesis of new enzyme. 

Diphenhydramine hydrochloride, 3,173 Diphenoxylate hydrochloride, 7,149 Disulflram, 4, 168 Dobutamine hydrochloride, 8,139 Droperidol, 7,171 Echothiophate iodide, 3,233 Epinephrine, 7, 193 Ergotamine tartrate, 6,113 Erythromycin, 8,139 Erythromycin estolate, 1, 101 2, 573 Estradiol valerate, 4,192 Ethambutol hydrochloride, 7,231 Ethynodiol diacetate, 3,253 Fenoprofen calcium, 6,161 Flucytosine, 5,115 Fludrocortisone acetate, 3, 281 Fluorouracil, 2,221 Fluoxymesterone, 7,251 Fluphenazine enanthate, 2, 245 4,523 Fluphenazine hydrochloride, 2,263 4,518 Gluthethimide,5,139 Gramicidin, 8,179 Griseofulvin, 8,219 Halcinonide, 8,251 Halothane, 1, 119 2,573 Hexetidine, 7,277 Hydralazine hydrochloride, 8,283 Hydroflumethiazide, 7,297 Hydroxyprogesterone caproate, 4,209 Hydroxyzine dihydrochloride, 7,319 Iodipamide, 3,333 Isocarboxazid, 2, 295... 

Nakamura, M., Fukushima, H., and Kitagawa, S. (1976) Effect of amitriptyline and isocarboxazid on 5-hydroxytryptophan induced head twitches in mice. Psychopharmacology, 48 101-104. 

With most psychedelics, their activity can probably be considerably enhanced by prior (or possibly concomitant) use of a monoamine oxidase inhibitor (e.g., isocarboxazid (Marplan), nialamide (Niamid), phenelzine (Nardil), and tranylcypromine (Parnate)). Some compounds (e.g., DMT) which have no oral activity, can probably become orally active. These compounds are often prescribed as antidepressants, but it is not a good idea to use them frequently or in large doses. For antidotes to the hallucinogens see Amer. J. Hosp. Pharm. 30,80(1973). 

Isocarboxazid Boil 0.5 g with 5 ml H202 soln. (30%) and 10 ml NaOH soln. (20% w/v in DW) for 2 minutes. Cool, neutralize to litmus with HN03 and add sufficient DW to produce 40 ml. Test with the resulting solution. Complies with limit test for chlorides (25 ppm). 

Increased bilirubin levels are caused due to the intake of large doses of such drugs as chloroquine, vitamin K, sulpha-drugs, tetracyclines, paracetamol, nicotinic acid and monoamine oxidase inhibitors (e.g., iproniazid RP 1.0 nialamide RP 1.8 isocarboxazid RP 3.1 phenelzine RP 18 pheniprazine RP31 and tranylcypromine RP 45), where RP designates the Relative Potency based on the tiyptamine potentiation test. The elevated levels are due to hepatic injury, and... 

In general, aromatic primary amino moiety (i.e., Ar-NH2), as present in a host of sulphadrugs viz., succinyl sulphathiazole, sulphamethoxazole, sulphaphenazole and other potent pharmaceutical substances, for instance sodium or calcium aminosalicylate, isocarboxazid, primaquine phosphate, procainamide hydrochloride, procaine hydrochloride and dapsone react with sodium nitrite in an acidic medium to yield the corresponding diazonium salts as expressed below ... 

Theory The estimation is based on the fact that isocarboxazid undergoes rapid cleavage in acidic medium to produce benzylhydrazine. The latter reacts quantitatively with nitrous acid (NaN02 and HC1) to give rise to benzylazide. The various reactions involved are expressed as follows ... 

A -Alkylhydrazides also undergo metabolic hydrolysis. Thus, the major metabolites of the monoamine oxidase inhibitor isocarboxazid (4.264)... 

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