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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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.[1]


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