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.