Comparison of prizidilol hydrochloride (SK & F 92657), a new antihypertensive agent with beta‐adrenoceptor antagonist and vasodilator activity with propranolol and hydralazine in normal volunteers.

Abstract

1 Some cardiovascular pharmacology of prizidilol hydrochloride, a new antihypertensive compound with precapillary vasodilator and ,3-adrenoceptor antagonist activity, in man is described.2 To investigate further the pharmacological profile of this drug the effects of a single oral dose of 400 mg prizidilol hydrochloride were compared with propranolol 40 mg in combination with either 25 mg or 50 mg of hydralazine for up to 6 h after dosing, in a placebo controlled study in eight healthy subjects. 3 Prizidolol hydrochloride significantly reduced supine and standing diastolic blood pressure and was more effective than propranolol combined with either dose of hydralazine in this respect. 4 Supine heart rate was significantly increasd after prizidilol hydrochloride, but was not significantly changed after propranolol combined with either dose of hydralazine. The reasons for the increase in supine heart rate after prizidolol are discussed. 5 /8-adrenoceptor antagonism was assessed in terms of inhibition of exercise induced increases in heart rate and systolic blood pressure. At the doses used, prizidolol hydrochloride was less effective than propranolol and hydralazine combined, particularly during the first 3 h after dosing.

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

“…In this study, a single oral dose of 400 mg prizidilol hydrochloride significantly reduced sitting and standing diastolic blood pressure without altering systolic blood pressure or heart rate. Similar observations were made by Steiner et al (1981) and Bell et al (1979), although the latter demonstrated a significantly increased supine heart rate after 400 mg oral prizidilol. However, Pitcher et al (1982) found no increase in -.0 heart rate after 200 mg oral prizidilol and concluded that this dose caused /3-adrenoceptor antagonism without the vasodilatation apparent at higher doses.…”

“…The doses were chosen on the basis of studies which have shown the /8-adrenoceptor blocking activity of 400 mg prizidilol to correspond to approximately 40 mg propranolol (Pitcher et al, 1979;Steiner et al, 1981). The following measurements were made on each subject on all trial days pre-treatment (baseline), and then repeated hourly for 8 h after dosing.…”