Neuroleptic influence on hyperthermia induced by 5-hydroxytryptophan and p-methoxy-amphetamine in MAOI-pretreated rabbits
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5-Hydroxytryptophan (5-HTP) and p-methoxyamphetamine (p-MA) induced dose-dependent, lethal hyperthermia when applied intravenously to monoamine oxidase inhibitor (MAOI) pretreated rabbits. The time course of hyperthermia and the doses required to induce hyperthermia varies between the two substances. Results with α-MT and PCPA suggest that 5-HTP hyperthermia depends on 5-HT formation, release of endogenous 5-HT, and the presence of catecholamines, whereas p-MA-induced hyperthermia most likely is a result of indirect 5-HT release.
Some neuroleptics (piflutixol, spiroperidol and methiotepine) are extremely potent inhibitors of the induced hyperthermia. Also the 5-HT receptor blocking agent methergoline antagonizes hyperthermia induced by the two substances in rather low doses. On the other hand cis (Z)-flupenthixol is a very weak antagonist of 5-HTP but a more potent inhibitor of p-MA hyperthermia. It is concluded that both 5-HT and catecholamine (dopamine) receptor blockade is required to antagonize 5-HTP hyperthermia and that antagonism of p-MA induced hyperthermia is primarily a result of influence on the 5-HT system.
Key wordsNeuroleptics 5-HT-antagonism Hyperthermia 5-HTP p-Methoxyamphetamine Rabbits
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