Antihypertensive and hemodynamic actions of SCH 19927, the R,R-isomer and labetalol

Abstract

SCH 19927, one of the four chiral forms of labetalol, is approximately 4 times as potent as a beta adrenergic receptor blocker as the parent racemate, but is only one-third as potent in blocking alpha receptors. The present report describes its antihypertensive and hemodynamic actions. SCH 19927 and labetalol lowered blood pressure in hypertensive rats and dogs. SCH 19927 was somewhat more effective at lower doses, but the two agents produced comparable responses at higher doses. Both reduced blood pressure and peripheral resistance and increased cardiac output in anesthetized dogs. Intraarterial injection in to the femoral vascular bed, either in the presence or absence of neurogenic vasoconstrictor tone, resulted in dose-related vasodilatation. In contrast, alpha blockers, e.g., phentolamine and prazosin, are essentially devoid of vasodilator activity in denervated beds. It is concluded that vasodilatation is largely responsible for the antihypertensive response to labetalol and particularly to SCH 19927. SCH 19927 is a potentially useful agent which would be expected to reduce pressure in humans by two complementary mechanisms, beta blockade and vasodilatation. It should possess less orthostatic potential than labetalol.