Inhibition of 5-hydroxytryptamine-mediated behaviour by the putative 5-HT2 antagonist pirenperone

The effect of pirenperone, a putative 5-HT2 receptor antagonist, on various 5-HT-mediated behavioural responses has been examined. The head twitch response in mice, induced by administration of carbidopa (25 mg/kg) followed by 5-hydroxytryptophan (5-HTP) (200 mg/kg), was inhibited in a dose-dependent manner by pirenperone, with an ED50 of 76 micrograms/kg. The appearance of head weaving, forepaw treading and hind-limb abduction, which followed the administration of tranylcypromine (5 mg/kg) plus L-tryptophan (100 mg/kg) or quipazine (50 mg/kg) to rats, was also inhibited by pretreatment with pirenperone (100 micrograms/kg). Pirenperone did not alter the rate of 5-HT synthesis in the rat brain. Whilst pirenperone (100 micrograms/kg) did decrease methamphetamine-induced locomotor activity in rats, a dose of haloperidol producing a similar inhibition of this response did not alter the 5-HT-mediated behaviour. It is suggested, therefore, that the currently used 5-HT-induced behavioural models are 5-HT2 receptor-mediated.