Effects of M6434, an orally active alpha 1-adrenoceptor agonist, on experimental postural hypotension in rabbits and dogs

Abstract

We examined the effects of M6434 on mean blood pressure and heart rate in conscious rabbits and dogs and on experimental models of postural hypotension in conscious rabbits and anesthetized dogs. M6434, given orally, elevated the mean blood pressure in conscious rabbits and dogs. The pressor effect of M6434 was more potent than that of midodrine, but the bradycardiac action of M6434 was weaker than that of midodrine. M6434 (1.0 and 3.0 mg/kg, p.o.) prevented the head-up tilt-induced reductions of mean blood pressure and cerebral tissue blood flow in conscious rabbits, and these effects of M6434 were about 3 times more potent than those of midodrine. In the postural hypotension of anesthetized dogs, M6434 at the doses more than 10 micrograms/kg, i.v. also produced the preventive effects on mean blood pressure and cerebral tissue blood flow. These effects of M6434 were about 10-30 times more potent than those of midodrine. These results show that M6434 possesses a potent hypertensive effect with a weaker bradycardiac action and suggest that M6434 may be a potential candidate for an anti-hypotensive agent that can prevent the deterioration of hemodynamics in postural hypotension.