Antagonism of L-5-hydroxytryptophan-induced head twitching in rats by lisuride: a mixed 5-hydroxytryptamine agonist-antagonist?
Lisuride antagonized L-5-hydroxytryptophan (5-HTP)-induced head twitches at doses lower than those sufficient to induce the serotonin (5-HT) syndrome. Among several other 5-HT agonists tested, only LSD and 1-(m-trifluoromethylphenyl)-piperazine (TFMPP) shared this paradoxical profile. Assessment of various dopamine (DA) agonists revealed a lack of correlation between DA-mediated stereotyped behavior (indicative of postsynaptic DA agonism) and blockade of 5-HTP-induced head twitches. Lisuride displaced specific ligand binding from putative S1a, S1b and S2 receptors at nanomolar concentrations, and other drugs that blocked 5-HTP-induced head twitches also displaced binding at S2 sites. It is proposed that lisuride may have agonist properties at S1a receptors mediating the 5-HT syndrome but antagonist properties at S2 receptors mediating 5-HTP-induced head twitching.
D006916:5-Hydroxytryptophan / Q000037:antagonists & inhibitors*; D000818:Animals; D004298:Dopamine / Q000502:physiology; D004873:Ergolines / Q000494:pharmacology*; D005277:Fenfluramine / Q000031:analogs & derivatives / Q000494:pharmacology; D008090:Lisuride / Q000494:pharmacology*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D009069:Movement Disorders / Q000139:chemically induced*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D012702:Serotonin Antagonists; D013239:Stereotyped Behavior / Q000187:drug effects; D009435:Synaptic Transmission
D004873:Ergolines; D011954:Receptors, Dopamine; D012702:Serotonin Antagonists; D005277:Fenfluramine; C037762:1-(3-trifluoromethylphenyl)-2-propanol; D008238:Lysergic Acid Diethylamide; D006916:5-Hydroxytryptophan; D008090:Lisuride; D004298:Dopamine