1 The present study investigated the ability of neuroleptic drugs to induce hypothermia in mice when they were administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.). 2 Twelve neuroleptics belonging to five chemical classes including phenothiazines, butyrophenones, benzamides, thioxanthenes and diphenylbutylpiperidines were injected i.p. All of them, except benzamides, induced a dose-dependent decrease in rectal temperature. 3 Neuroleptics were administered i.c.v. via cannulae previously implanted in mice to determine whether this response might have a central origin. None of the drugs tested induced hypothermia at doses which did not produce toxic effects. These negative results suggest that neuroleptics act to elicit hypothermia via a peripheral, rather than a central mechanism. 4 Since some neuroleptics possess a-adrenolytic properties which could induce hypothermia by promoting vasodilatation, we attempted to antagonize the hypothermia produced by peripheral administration of two neuroleptics with phenylephrine, an a-adrenoceptor agonist that does not cross the blood-brain barrier. The hypothermia induced by both chlorpromazine and haloperidol was attenuated by phenylephrine, supporting the view that peripheral a-adrenoceptors may mediate neuroleptic-induced hypothermia.

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