A quantitative assessment of CNS sympatho-inhibition produced by psychotropic drugs.
As one index of sympathetic reactivity, electrodermal responses (EDR) were evoked from central (hypothalamic) and peripheral (ulnar nerve) sites in pentobarbital-anesthetized cats. When compared with intravenous chlorpromazine (ED50 approximately 1.0 mg/kg), only thioridazine, trifluoperazine, and pimozide were less potent than chlorpromazine in reducing the amplitude of these centrally-evoked sympathetic-cholinergic responses. Perphenazine and methotrimeprazine (a non-neuroleptic phenothiazine) were about twice as potent as chlorpromazine. Haloperidol and triflupromazine were about 5 times as potent and chlorprothixine was more than 10 times as potent. None of these agents reduced the peripherally-evoked electrodermal response, indicating a CNS mode of action. Diazepam was without effect at either site. In addition, pretreatment with yohimbine (0.5 mg/kg. i.v.) did not significantly alter the ED50 for any of the above drugs. These results demonstrate that all of the phenothiazines and non-phenothiazine neuroleptics tested produce a dose-dependent central sympatho-inhibition and that diazepam does not. The results also suggest that there is no significant correlation between central sympatho-inhibition and the antipsychotic potency of these compounds and that their depression of central sympathetic outflow is independent of alpha-adrenergic mechanisms in the CNS.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects*; D002746:Chlorpromazine / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D008297:Male; D010525:Peripheral Nerves / Q000187:drug effects; D011619:Psychotropic Drugs / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects; D012879:Skin Physiological Phenomena; D013564:Sympathetic Nervous System / Q000187:drug effects*
D014150:Antipsychotic Agents; D011619:Psychotropic Drugs; D001285:Atropine; D003975:Diazepam; D002746:Chlorpromazine