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Keywords:

5-Hydroxytryptophan, Animals, Anti-Anxiety Agents, Anxiety, Chlordiazepoxide, Diazepam, Disease Models, Animal, Histamine H2 Antagonists, Humans, Lysergic Acid Diethylamide, Male, Motor Activity, Piperidines, Pyrimidines, Rats, Rats, Inbred Strains, Ritanserin, Serotonin Antagonists, 11 Medical and Health Sciences, 17 Psychology and Cognitive Sciences, Psychiatry, 5202 Biological psychology

Abstract:

The newly synthesized compound and putative 5-HT2 antagonist ritanserin, but not the structurally related compound R 56413, resembles pirenperone in that it acts as a pure antagonist in an LSD-saline drug discrimination assay in the rat. Ritanserin exceeded pirenperone in terms of behavioral specificity; the lowest effective dose of ritanserin in antagonizing LSD was one order of magnitude higher than that of pirenperone, but the compound depressed rate of operant responding only at doses that were about 1000-fold higher than those at which pirenperone was effective. Ritanserin exerted effects in an open field test which were reminiscent of anxiolytic drug activity in the rat; its effects were greater than those of pirenperone, R 56413 and the benzodiazepines chlordiazepoxide and diazepam. The results of experiments on antagonism of 5-HT-induced hypothermia and of the 5-HTP-induced head-twitch response fail to support the possibility that the putative anxiolytic effects of ritanserin in the rat can be ascribed simply to a pharmacologically defined action at 5-HT receptors.