Antihypertensive and hypotensive actions of atiprosin (AY-28,228) in rats, dogs, and monkeys.

Atiprosin, a chemically novel octahydro-pyrazino-pyrido-indole, exerts antihypertensive effects in spontaneously hypertensive, deoxycorticosterone acetate hypertensive, and renal-hypertensive rats over a dose range of 0.1-10 mg/kg per os (p.o.). In terms of relative potency, atiprosin was calculated to be seven to fifteen times less potent than prazosin, five to sixteen times more potent than ketanserin, and 14-25 times more potent than indoramin, depending on the hypertensive model examined. Atiprosin had good oral bioavailability (p.o./i.v. ratio = 1.25), and there was no evidence from rat studies for tolerance on repeated administration. The compound also exerted hypotensive effects in normotensive rats and monkeys at 1-10 mg/kg p.o.; in neither species was there evidence of drug-induced tachycardia. Experiments in anesthetized dogs suggest that atiprosin may be similar to prazosin with respect to its liability to produce orthostatic hypotension as a side effect.