Partial and complete blockade of 5‐hydroxytrytophan (5‐HTP)‐induced head twitches in the rat: A study of ritanserin (R 55 667), risperidone (R 64 766), and related compounds

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Abstract
A series of test compounds were studied for their ability to inhibit and block the head‐twitch response to either intraperitoneal (i.p.) 5‐hydroxytryptophan (5‐HTP) or intravenous (i.v.) mescaline in rats. Both responses were found to be sensitive to serotonin S2 antagonists, and there was very good agreement between the inhibitory doses in both tests, particularly for the selective serotonin S2 antagonists ritanserin and seganserin. However, these two compounds did not block the 5‐HTP response, although they completely abolished the mescaline response. In contrast, the mixed serotonin‐dopamine‐norepinephrine antagonist risperidone was a potent blocker of both responses. The use of various antagonists and the combination treatments of ritanserin with haloperidol or prazosin indicated that the 5‐HTP response is abolished when potent serotonin S2 antagonism is associated with antagonistic activity on either dopamine D2 or α1 receptors.