Some cardiovascular effects of ST-91 and clonidine.
St-91, 2(2,6-diethylphenylamino)-2-imidazoline, is a clonidine derivative which does not penetrate the blood-brain barrier. In spontaneously hypertensive (SH) rats is acutely increased arterial pressure and reduced heart rate while at 8 to 12 h after oral administration, it slightly lowered arterial pressure. In contrast, clonidine had acute antihypertensive activity at all doses used. By intracerebroventricular administration to SH rats, both drugs (St-91 and clonidine) reduced arterial pressure and heart rate; in this respect, clonidine was more potent then St-91. Cardiac acceleration induced by low frequency electrical stimulation of right cardiac sympathetic nerves in anesthetized and vagotomized dogs was reduced by St-91 at the same doses by clonidine. Phenoxybenzamine, phentolamine and desipramine antagonized the inhibitory effects of St-91 on electrically induced cardiac acceleration. It was concluded that St-91, like clonidine, stimulates inhibitory alpha-adrenergic receptors at the sympathetic nerve endings but, unlike clonidine, is substantially devoid of acute antihypertensive activity. This suggests that stimulation of peripheral presynaptic inhibitory alpha-adrenergic receptors is not likely to represent the sole mechanism of antihypertensive action of clonidine.
D000284:Administration, Oral; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000031:analogs & derivatives; D003891:Desipramine / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D014628:Vagotomy
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D010643:Phenoxybenzamine; C011266:ST 91; D003000:Clonidine; D003891:Desipramine; D010646:Phentolamine