Mescaline‐induced head‐twitches in the rat: An in vivo method to evaluate serotonin S2 antagonists

An intravenous dose of 20.0 mg/kg of mescaline reliably caused head-twitching in rats. Many drugs with different pharmacological actions were tested for their ability to block this response, including numerous serotonin antagonists and two selective S2 antagonists: ketanserin and pirenperone. The same compounds were also examined in six in vivo tests measuring antagonism at serotonin, dopamine, norepinephrine, histamine, or acetylcholine sites. Inhibition of mescaline-induced head-twitches did not correlate with blocking dopamine, norepinephrine, histamine, or acetylcholine receptors, but did correlate with in vivo antagonism of tryptamine and 5-hydroxytryptophan, and with inhibition of 3H-spiperone binding to rat prefrontal cortex in...

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Abstract

Abstract An intravenous dose of 20.0 mg/kg of mescaline induced a reproducible head‐twitch response in rats. Drugs with very different pharmacological activities were tested for potential inhibition of this response. Among these drugs were a large number of serotonin antagonists, including several members of the recently described selective S 2 antagonists of which ketanserin (a potent vascular S 2 antagonist) and pirenperone (a pure LSD antagonist) are two prototypes. The same compounds were further studied in six in vivo tests in rats; these tests presumably measure antagonism at sites responsive to serotonin, dopamine, norepinephrine, histamine, or acetylcholine. A large number of test compounds inhibited mescaline‐induced head‐twitches. Although it was often associated with it, this activity did not correlate with any of the following effects: antagonism of apomorphine, norepinephrine, compound 48/80, physostigmine, or with mydriatic activity. Antagonism of mescaline did correlate, however, with in vivo antagonism of tryptamine and 5‐hydroxytryptophan, and with inhibition of 3 H‐spiperone binding to the rat prefrontal cortex in vitro. It is concluded that inhibition of mescaline‐induced head‐twitches in the rat is a valid measure of serotonin S 2 antagonist activity, also for those compounds whose primary activity occurs at dopamine, norepinephrine, histamine, or acetylcholine receptors. Ketanserin, pirenperone, and several chemically related compounds are very potent mescaline antagonists.