The head-twitch response to intraperitoneal injection of 5-hydroxytryptophan in the rat: antagonist effects of purported 5-hydroxytryptamine antagonists and of pirenperone, an LSD antagonist.
The putative 5-hydroxytryptamine (5-HT) antagonists 2-bromo-LSD, cinanserin, cyproheptadine, pizotifen, methysergide, metitepine, mianserin and metergoline were found to reduce the frequency of the head-twitch response induced by intraperitoneal injections of 320 mg/kg of 5-hydroxytryptophan (5-HTP) in the rat. The antagonist dose-effect curve of these agents was biphasic. It consisted of an initial, steep, phase and a subsequent, shallower, phase. Analysis of the data by means of quantitative and quantal methods yielded different rank orders of potency of antagonist drugs. Only pirenperone, a drug identified earlier as a pure antagonist, produced a simple, monophasic dose-effect curve in antagonizing the effects of 5-HTP. The antagonist effects of pirenperone, and the first phase of the curve of the putative 5-HT antagonists, may reflect antagonist activity at 5-HT2 receptors. The data are consistent with earlier behavioural evidence that the putative 5-HT antagonists act complexly as mixed agonist-antagonists; only pirenperone exerted behavioural effects that suggest it to be a pure antagonist.
D006916:5-Hydroxytryptophan / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*
D010880:Piperidines; D012702:Serotonin Antagonists; D006916:5-Hydroxytryptophan; C034177:pirenperone