SK&F 92657, a Novel Antihypertensive Acting by Precapillary Vasodilatation and β-Adrenoreceptor Blockade

Abstract

1. The properties of a new antihypertensive agent, SK&F 92657, DL-3-[2-(3-t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazine, have been studied. 2. The compound caused a sustained fall in blood pressure in several species as a result of precapillary vasodilatation, particularly in the renal and coronary vasculatures. 3. The beta-adrenoreceptor-blocking actions of SK&F 92657 prevent reflex cadiac stimulation.

Assessment in man of SK & F 92657, a novel compound with vasodilator and beta‐adrenoceptor blocking activity [proceedings]

“…The pharmacokinetics of propranolol were compared with those of the f51-adrenoceptor selective blocker SL 75212 which has similar physicochemical characteristics (Davies & Turner, 1979) but which, unlike propranolol, undergoes little 'first-pass' loss (F = 80%, Bianchetti, Gomeni, Kilborn, Morselli, Taylor & Warrington, 1979 (dl-3-[2-(3-t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazine) is a new compound which has been shown to combine ,B-adrenoceptor blockade with hydralazine-like vasodilatation both in animals (Taylor, Roe & Slater, 1979) and in man (Collier & Pitcher, 1980). In the present study the P-adrenoceptor blocking activity in six normal subjects of a single oral dose of 200 mg SK & F 92657 was assessed and compared to that of placebo and that of propranolol 40 mg, by measuring heart rate and blood pressure responses to intravenous infusions of isoprenaline at intervals up to 7 h after drug administration.…”

An assessment of beta‐adrenoceptor blockade in man by SK & F 92657, a new drug with combined vasodilator and beta‐adrenoceptor blocking actions, and comparison with propranolol [proceedings]

“…Recumbent and standing blood pressure and heart rate were measured before dosing and at 30 min intervals for eight h after dosing. SK & F 92657 (dl-3-[2-(3-t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazine) is a new compound which has been shown to combine ,B-adrenoceptor blockade with hydralazine-like vasodilatation both in animals (Taylor, Roe & Slater, 1979) and in man (Collier & Pitcher, 1980 (Taylor, Roe & Slater, 1979). We report here its effects on peripheral capacitance and resistance vessels in man.…”

Sustained Decreases in Systemic Blood Pressure Do Not Cause Ocular Hypotension

“…In order to clarify the implied rela tionship between systemic and ocular hypo tension, it was considered worthwhile to evaluate the effect of a substantial and sus tained decrease in blood pressure on intra ocular pressure. The vasodilator hydralazine [10] and prizidilol, a dual vasodilator-Padrenoceptor antagonist [11][12][13], provided appropriate agents for these investigations because of their lack of effect on intraocular pressure when applied topically to the eye.…”