Studies on the cardiovascular depressor actions of ST 91--an analogue of clonidine.
St 91 is an analogue of the alpha-adrenoceptor agonist and antihypertensive agent clonidine. I.v. infusion of St 91 (8 microgram/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 microgram/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 microgram/kg over 2 min) into the vertebral artery (i.a. vert.) produced dose-dependent hypotension and bradycardia only, which were reversed by piperoxan (300 microgram/kg, intracisternal). There was no significant difference in the potency of St 91 when given i.a. vert. or i.c.m. (5--20 microgram/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.
D000818:Animals; D002415:Cats; D002946:Cisterna Magna; D003000:Clonidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003864:Depression, Chemical; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007267:Injections; D007269:Injections, Intra-Arterial; D008297:Male; D014711:Vertebral Artery
D003000:Clonidine