Studies on the diuretic effect of haloperidol in adult rats

Abstract

An increase in urinary flow has been observed in rats during cataleptic response to haloperidol. The present experiment was carried out to study the mechanism of haloperidol-induced diuresis. Wistar-Imamichi adult female rats were injected i.p. with haloperidol in a dose of 0.1, 1 or 10 mg/kg, and the time course of changes in urine volume was observed. The dose-dependent diuretic effect of 1 or 10 mg/kg haloperidol was significant from 4 hr afterward, and the haloperidol-induced diuresis was prevented by pretreatment with phenoxybenzamine, prazosin or yohimbine. Chlorpromazine but not spiperone and pimozide induced a significant increase in urine volume, though the effect of chlorpromazine was less marked as compared with that of haloperidol. Clonidine in a dose of 0.125~1.0 mg/kg enhanced urine flow markedly from 30 min, and the same a-adrenergic blockers were also effective in blocking the diuretic effect of clonidine. Urinary osmolarity in 1 mg/kg haloperidol-and 0.125 mg/kg clonidine-treated rats decreased significantly, whereas only clonidine stimulated urinary Na and K excretion. Plasma osmolarity and negative free water clearance did not change in both haloperidol- and clonidine-treated rats. The present results suggest that the haloperidol-induced diuretic effect could be due to the central α-adrenoceptor blocking action of haloperidol. © 1986, The Japanese Pharmacological Society. All rights reserved.