Monoamine oxidase inhibitors isoniazid

Monoamine Oxidase Inhibitors. MAOIs inactivate the enzyme MAO, which is responsible for the oxidative deamination of a variety of endogenous and exogenous substances. Among the endogenous substances are the neurotransmitters, norepinephrine, dopamine, and serotonin. The prototype MAOI is iproniazid [54-92-2] (25), originally tested as an antitubercular dmg and a close chemical relative of the effective antitubercular, isoniazid [54-85-3] (26). Tubercular patients exhibited mood elevation, although no reHef of their tuberculosis, following chronic administration of iproniazid. In... 

The first generation of antidepressants, MAO (monoamine oxidase) inhibitors, inhibited neurotransmitter degradation by inhibiting monoamine deoxidase, a flavin containing enzyme, found in the mitochondria of neurons and other cell types, that oxidatively deaminates naturally occurring sympathomimetic monoamines, such as norepinephrine, dopamine, and serotonin within the presynapse. In 1952, isoniazid and its isopropyl derivative, iproniazid (1), were developed for the treatment of tuberculosis, where it was subsequently found that these agents had a mood enhancing effect on... 

The positive effects of the monoamine oxidase inhibitor isoniazid and the amine reuptake blocker imipramine were both discovered by accident. Isoniazid was being used as an antitubercular drug when patients reports of elation led Nathan Kline to test and to demonstrate its antidepressant power. Ronald Kuhn had synthesized imipramine, a tricyclic molecule, as a possible me-too analog of chlorpromazine. When Kuhn found that it had little or no antipsychotic potential, he tried it out on depressives, and voila They got better. After a while, that is. As with isoniazid, imip-ramine s antidepressant action was evident only after one to four weeks of administration. 

Polasek TM, Elliot DJ, Somogyi AA, et al. An evaluation of potential mechanism-based inactivation of human drug metabolizing cytochromes P450 by monoamine oxidase inhibitors, including isoniazid. Br J Clin Pharmacol 2006 61(5) 570-584. 

Isoniazid inhibits monoamine oxidase, and hence reduces tyramine metabolism this effect is enhanced by co-administration of other monoamine oxidase inhibitors... 

If isoniazid is implicated in optic neuropathy or other neurologic signs, then pyridoxine (vitamin Bg), 25 to 100 mg/day, may be used. Prophylactic administration of this agent can be combined with isoniazid and monoamine oxidase inhibitor therapy. 

Drug Interactions Barbiturates combine with other CNS depressants to cause severe depression ethanol is the most frequent offender, and interactions with first-generation antihistamines also are common. Isoniazid, methylphenidate, and monoamine oxidase inhibitors also increase the CNS-depressant effects. Other prominent drag interactions occin as a result of the induction of hepatic drug-metabolizing enzymes by barbiturates see above). 

Nervous system Seizures have been attributed to flumazenil [104, 105, 106, 107, 108, 109, 110, 111 ], including status epilepticus [112, 113 ], which can be fatal. However, it has been suggested that seizures are not a toxic effect of flumazenil, but are in many cases instead due to unmasking of the anticonvulsant effect of the benzodiazepine or to a severe benzodiazepine-withdrawal syndrome furthermore, in some cases they may be due to other drugs taken at the same time, such as tricyclic antidepressants [1143]. Thus, it has been recommended that flumazenil should not be given to patients who have used benzodiazepines for seizure disorders or to patients who have taken other drugs that increase the risk of seizures (e.g. bupropion, ciclosporin, cocaine, cyclic antidepressants, isoniazid, lithium, methylxanthines, monoamine oxidase inhibitors, and propoxyphene). 

Piperonyl butoxide, isoniazid, and SKF 525A and related chemicals are inhibitors of various xenobiot-ic-metabolizing enzymes. For instance, piperonyl butoxide increases the toxicity of pyrethrum (an insecticide) by inhibiting MFO activity in insects that detoxifies this agent. Isoniazid, when taken along with phenytoin, lengthens the plasma half-life of the antiepileptic drug and increases its toxicity. Iproniazid inhibits monoamine oxidase and increases the cardiovascular effects of tyramine, which is found in cheese and which is normally readily metabolized by the oxidase. 

The effect of inhibitors was investigated. Monoamine oxidases are inhibited by iproniazid but not by isoniazid. The plasma enzyme was inhibited by both reagents. Diamine oxidases are inhibited by cyanide, carbonyl reagents, and by isoniazid. The amine oxidase of plasma was inhibited by all three reagents. Therefore, although the substrate specificity of this enzyme tends to be more closely related to that of monoamine oxidase, its inhibition pattern resembles that of the diamine oxidases. 

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