Monoamine oxidase inhibitors chlorpromazine

Rare, familial hyperthermia (41 °C) associated with inhalation anaesthetics, muscle relaxants, tricyclic antidepressants, phenothiazine neuroleptics (particularly chlorpromazine) monoamine oxidase inhibitors and haloperidol. 

It can be argued that the introduction of lithium salts into the practice of psychiatry in 1949 heralded the beginning of psychopharmacology, as it predated the discovery of chlorpromazine, imipramine, monoamine oxidase inhibitors and resperine. Lithium came into clinical use serendipitously, the Australian psychiatrist Cade having by chance given it to a small group of manic patients and found that it had beneficial effects. 

Morphine and other opioids exhibit intense sedative effects and increased respiratory depression when combined with other sedatives, such as alcohol or barbiturates. Increased sedation and toxicity are observed when morphine is administered in combination with the psychotropic drugs, such as chlorpromazine and monoamine oxidase inhibitors, or the anxiolytics, such as diazepam. 

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. 

In the otherwise unmedicated animal, imipramine and its related compounds have even fewer behavioural effects than the monoamine oxidase inhibitors. Such changes as have been recorded, using conditioned avoidance and escape techniques, suggest that behaviourally the drugs resemble the tranquillizers . Chlorpromazine and amitriptyline have similar depressant effects on the electrical activity of the brain, reducing the frequency of the spontaneous rhythms. Amitriptyline has been used for treating patients in whom depression and anxiety occur together. 

Grantiiam J, Neel W, BrownR.W. Toxicity reveised. Reversal of imipramine-monoamine oxidase inhibitor induced toxicity hy chlorpromazine. J Kans Med Soc (1964) 65,279-80. 

Section B (Fig. 17) shows some commonly used drugs which are electroactive. The a-methyltryptamine was detected at + 0.8 V by Marsden (1980) in 5-HT studies. Several monoamine oxidase inhibitors are electroactive, but there is so far no evidence that they can be detected in vivo and, even if they are, it is at potentials sufficiently positive not to interfere with most studies. Chlorpromazine and haloperidol have solution Ep values about + 0.6 V and + 0.7 V, respectively. Clozapine oxidizes at about + 0.4 V. Since neuroleptics (and other drugs) are extensively metabolized by the time they appear in significant concentrations in the CNS, the potentials of the parent compounds may not be too relevant—but no data are available for metabolites. In any event, there is no evidence that any of these drugs are detected in CNS voltammetry. 

Often a single drug will have many metabolites including some which have effects similar to the parent (cyclosporin, chlorpromazine). Microsomal drug metabolism can be stimulated by medications such as the barbiturate phenobarbital or by cigarette smoke. Metabolism may be slowed by medications such as the monoamine oxidase inhibitors which are used in treatment of psychiatric disease. There are genetic and sex-related differences as well as age-related effects which may affect an individual patient s metabolism. 

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