Studies on the cardiovascular depressor actions of St 91 — an analogue of clonidine

Abstract

St 91 is an analogue of the α-adrenoceptor agonist and antihypertensive agent clonidine. I.v. infusion of St 91 (8 μg/kg/min, 2 min) produces an immediate but transient pressor response and a prolonged bradycardia but, unlike clonidine, it produces no hypotension, allegedly because this drug does not penetrate the C.N.S. It was found that, after pretreatment with phenoxybenzamine (1.5 mg/kg, i.v.) an infusion of St 91 (8 μg/kg/min, 2 min) produced a much diminished pressor response and a later small hypotension, while still causing the same degree of bradycardia. Infusion of St 91 (4–16 μg/kg over 2 min) into the vertebral artery (i.a. vert.) produced dose-dependent hypotension and bradycardia only, which were reversed by piperoxan (300 μg/kg, intracisternal). There was no significant difference in the potency of St 91 when given i.a. vert. or i.c.m. (5–20 μg/kg) and the dose-response curves for hypotension and bradycardia were parallel, although the onset of effects was more rapid via the vertebral route. It is suggested that St 91 can cross the blood-brain barrier although why no hypotension is observed after i.v. administration still remains obscure.