Pharmacodynamic Effects of a New Antihypertensive Drug, Catapres (ST-155)

Abstract

Catapres is a new imidazoline compound with potent antihypertensive properties. Significant reduction in blood pressure occurs between 1 and 4 hours after oral administration, with the peak effect occurring at 2 to 4 hours and the antihypertensive effect extending for 6 to 10 hours. Blood pressure is reduced in both the supine and erect positions, although the orthostatic response is the more prominent. Cardiac output is reduced moderately in both the supine and erect positions. Peripheral vascular resistance is also reduced, particularly in the erect posture. Accordingly, the cardiac hemodynamic findings suggest that the antihypertensive effect of Catapres is related to the combination of reduction in cardiac output plus decrease in peripheral resistance. Renal blood flow and glomerular filtration rate are preserved in both the supine and erect positions following Catapres administration. Contrasting with the preservation of renal blood flow and glomerular filtration rate, however, is the marked reduction in sodium chloride excretion which follows acute administration of the drug. The clinical utility of the drug was demonstrated in the chronic outpatient study. Although Catapres administered alone exerted only modest antihypertensive effects, a markedly enhanced antihypertensive response was achieved when the drug was combined with a potent oral diuretic, with 80% of patients so treated achieving significant blood pressure reduction in both the supine and erect positions.