Investigation of a combined arteriolar dilator and beta‐adrenoceptor antagonist (SK & F 92657) in the peripheral vessels of man.

Abstract

1 SK & F 92657 is a new compound which in animals has both precapillary vasodilator and beta‐adrenoceptor blocking activity. The effects of the drug on forearm blood flow and dorsal hand vein distensibility have been studied in healthy volunteers. 2 Forearm blood flow was measured by venous occlusion plethysmography. The drug was infused directly into a brachial artery. The effects of SK & F 92657 on resting flow and on the dose‐response relationship for intra‐arterial isoprenaline were studied. 3 Venous distensibility was measured in the large veins on the back of the hand. The drug was infused directly into a selected vein and its effects on resting tone and on the responses to noradrenaline and to isoprenaline were investigated. 4 Intra‐arterial infusion of SK & F 92657 over 2 min caused a dose‐dependent increase in forearm blood flow which developed gradually to reach a maximum after approximately 40 min. Infusion into dorsal hand veins at 100 ng/min and 500 ng/min had no dilator effect in veins preconstricted with noradrenaline. At higher doses SK & F 92657 potentiated the constrictor effect of noradrenaline. 5 In both veins and arteries SK & F 92657 attenuated the dilator effects of isoprenaline. The drug had no effect on the venodilator effects of bradykinin, histamine or sodium nitroprusside. 6 The pattern of response of these vessels to locally infused SK & F 92657 is exactly that expected of a drug combining the properties of hydralazine‐like vasodilatation and beta‐adrenoceptor blockade. Furthermore, in the arterioles, both properties were manifest at the same dose.

Cardiovascular effects in man of intravenous prizidilol hydrochloride (SK&F 92657); a new antihypertensive agent.

“…This may be due to the route of administration. Collier & Pitcher (1980) found that at low doses of 100 and 500 ng/min, intravenously administered prizidilol hydrochloride attenuated the dilator effects of locally infused isoprenaline on vessel walls. At doses of 400 ,ug and 1600 ,ug administered intra-arterially, dose-dependent vasodilatation was demonstrated, evidenced by mean increases in forearm blood flow of 59% and 40.3% respectively.…”

“…Prizidilol hydrochloride, dl-3-[2-(3-t-butylamino-2-hydroxypropoxy) phenyl-] 6-hydrazinopyridazine (SK&F 92657), is a new blood pressure lowering agent with both pre-capillary vasodilator and /3-adrenoceptor blocking activities whose hypotensive properties have been investigated in animal and man (Taylor, Roe & Slater, 1979;Bell et al, 1980;Collier & Pitcher, 1980). Experiments in anaesthetised rats, cats and dogs have shown that intravenous prizidilol hydrochloride (2-4 mg/kg) causes pronounced peripheral vasodilatation.…”

Comparison of the effects of prizidilol and propranolol on renal haemodynamics at rest and during exercise.

“…Prizidilol (SK&F 92657) is a new effective antihypertensive agent which shows both 13-adrenoceptor blocking and vasodilating activities (Taylor et al, 1980;Collier & Pitcher, 1980;Pitcher et al, 1982). The drug, in the long term, induces a favourable haemodynamic pattern in that it lowers blood pressure levels without modifying heart rate and cardiac output both at rest and during exercise (Lund-Johansen & Omvik, 1982).…”

Pulmonary effects in man of oral prizidilol hydrochloride (SK&F 92657), a new antihypertensive agent.

“…Prizidilol hydrochloride, dl-3-[2-(3-t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazine (SK &F92657) is a new hypotensive agent which combines the properties of pre-capillary vasodilatation and ,f-adrenoceptor blockade (Bell etal., 1979;Collier & Pitcher, 1980;Taylor et al, 1979). It is well recognised that ,8-adrenergic receptor blocking drugs cause bronchoconstriction which may lead to symptoms of airflow obstruction (McNeil, 1964).…”