Central antiserotonergic and antidopaminergic action of pirenperone, a putative 5-HT2 receptor antagonist.
Pirenperone, an antagonist of 5-HT2 but not 5-HT1 receptors, has been studied for its central antiserotonergic and antidopaminergic activity. Pirenperone (0.00525-0.1 mg/kg) antagonized dose-dependently stimulation of the hind limb flexor reflex in spinal rats induced by LSD, quipazine or fenfluramine, and hyperthermia induced by serotonin (5-hydroxytryptamine; 5-HT)-like drugs (1-5-hydroxytryptophan, fenfluramine, p-chloroamphetamine, 1-/m-chlorophenyl/-piperazine, quipazine) in heat-adapted rats. Pirenperone also counteracted tryptamine-induced convulsions in rats (ID50 = 0.87 mg/kg); however, this action was weaker than that of metergoline (ID50 = 0.22 mg/kg). Pirenperone (0.1-1.6 mg/kg) produced sedation in mice and rats, and-in doses of 0.4-6.4 mg/kg-catalepsy in rats. Given in doses ranging from 0.1 to 1.6 mg/kg, pirenperone antagonized d-amphetamine-induced locomotor hyperactivity in mice and rats, the hyperactivity induced by apomorphine in rats, apomorphine- or d-amphetamine-induced stereotypy in rats and stimulation of the hind limb flexor reflex induced by the alpha-adrenoceptor agonist-clonidine. Pirenperone (6.4 mg/kg) significantly attenuated apomorphine (1 mg/kg)-induced hypothermia in mice. The results obtained indicate that pirenperone may be regarded as a relatively specific antagonist of the 5-HT2 receptor only when it is employed in very low doses (less than 0.1 mg/kg). Used in higher doses (greater than 0.1 mg/kg), it behaves like a typical neuroleptic, i.e. like a dopamine antagonist with antiserotonergic, antitryptaminergic and antiadrenergic properties.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects; D012640:Seizures / Q000517:prevention & control; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects; D014363:Tryptamines / Q000494:pharmacology
D010880:Piperidines; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014363:Tryptamines; C030820:tryptamine; D001058:Apomorphine; D003913:Dextroamphetamine; C034177:pirenperone