Some cardiovascular effects of ST-91 and clonidine

Abstract

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 admnistration to SH rats, both drugs (St-91 and clonidine) reduced by low frequency electrical rate; in this respect, clonidine was more potent than 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 as 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 α-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 α-adrenergic receptors is not likely to represent the sole mechanism of antihypertensive action of clonidine.