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

C. J. E. Niemegeers, Françis C. Colpaert, J.e. Leysen, F. Awouters, P. A. J. Janseen

Drug Development Research 1983 DOI: 10.1002/ddr.430030203 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Rats
Interventions mescaline ketanserin pirenperone
Dose 20.0 mg/kg
Topics Mescaline Serotonin
Keywords Ketanserin Pharmacology Spiperone Histamine Antagonism Serotonin antagonists In vivo Acetylcholine Ritanserin Norepinephrine Dopamine Tryptamine 5-HT Receptor Hallucinogen
Citations 58
Key findings Inhibition of mescaline-induced head-twitches in rats is a valid measure of serotonin S2 antagonist activity, and ketanserin, pirenperone, and related compounds are very potent mescaline antagonists.

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.

Comparable studies

Other preclinical and animal studies on mescaline, most cited first.

Study Year Design Participants
Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice 2020 Experimental study with dose-response experiments
Brain mechanisms of hallucinogens and entactogens Humans and rats 2001 Review
Effects of hallucinogenic agents mescaline and phencyclidine on zebrafish behavior and physiology Zebrafish (Danio rerio) 2012 Experimental study
Lysergic Acid Diethylamide- and Mescaline-Induced Attenuation of the Effect of Punishment in the Rat Rats 1976 Experimental study
Dihydrobenzofuran Analogues of Hallucinogens. 3. Models of 4-Substituted (2,5-Dimethoxyphenyl)alkylamine Derivatives with Rigidified Methoxy Groups Rats (trained to discriminate saline from LSD tartrate) and rat cortical and... 1996 In vivo drug discrimination assay and in vitro radioligand binding assay

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Mescaline Serotonin LSD