A centrally acting antihypertensive agent (R28935) not mediated via central alpha-adrenoreceptors

Intraventricular administration (i.c.v.) of R28935 (25 mug) produced a marked fall in blood pressure without any bradycardia in conscious renal hypertensive cats. This hypotensive effect was not antagonised by central administration of tolazoline (200 mug i.c.v.) or phentolamine (200 mug). However, these doses of alpha-adrenoreceptor blocking agents did antagonise the centrally mediated hypotensive actions of clonidine (20 mug i.c.v.) or alpha-methyl-dopa (1 mg i.c.v.). Infusions of R28935 in the perfused artery preparation did not modify the basal perfusion pressures or modify the vasoconstrictor actions of noradrenaline or 5-hydroxytryptamine. The results suggest that R28935, an analogue of pimozide, exerts a central hypotensive effect not mediated via central alpha-adrenoreceptors, and does not have any peripheral sympathomimetic action.