Pharmacological analysis of the myoclonus induced by 5-hydroxytryptophan in the guinea pig suggests the presence of multiple 5-hydroxytryptamine receptors in the brain

Myoclonus induced in guinea pigs by administration of l-5-hydroxytryptophan (5-HTP) appears to be due to stimulation of central 5-HT receptors. Dose-dependent myoclonus was induced by administration of 5-HTP (with carbidopa pretreatment), l-tryptophan and tryptamine (both with pargyline pretreatment). and also by N,N-dimethyltryptamine, 5-metoxy-N,N-dimethyltryptamine and d-lysergic acid diethylamide (LSD). The synthetic 5-HT agonists quipazine, MK-212 and 1-(m-trifluoromethylphenyl) piperazine, however, evoked only occasional myoclonus at toxic doses. Antagonists of 5-HT receptors differed markedly in their ability to inhibit 5-HTP-induced myoclonus; while methergoline and cyproheptadine were potent inhibitors, mianserin, methysergide and BW 501C67 only caused effective inhibition in large doses. Similarly, 5-HT re-uptake blockers showed different activities in potentiating the effects of a threshold dose of 5-HTP; myoclonus was greatly potentiated by chlorimipramine, paroxetine and Org 6582, while femoxetine, fluoxetine and desmethylimipramine were only weakly active.The lack of uniform effects of the 5-HT agonists, antagonists and re-uptake blockers studied is not attributable entirely to their variable actions on central 5-HT mechanisms, to their effects on other brain neuronal pathways, or to differences in cerebral penetration. The data may provide functional evidence for a multiplicity of cerebral 5-HT receptors.