Acute effects of prizidilol on blood pressure, heart rate, catecholamines, renin and aldosterone in essential hypertension.
Prizidilol is a new antihypertensive agent reported to possess combined precapillary vasodilator and betareceptor-blocking properties. To clarify the profile of the acute effects of prizidilol in man, a variable dose study was performed in 8 patients with benign essential hypertension. Blood pressure, heart rate, plasma renin activity, aldosterone, plasma and urinary catecholamines and electrolytes were determined at short intervals before and up to 23 h after oral administration of placebo and prizidilol 150, 300 and 600 mg. The 4 studies were performed at weekly intervals according to a Latin square design. Prizidilol produced dose-dependent decreases in supine and upright blood pressure, with an initial change after about 2 h and maximal effects from 4 to 8 h after drug ingestion. Following a high dose of prizidilol, supine mean blood pressure (average 128 mmHg prior to treatment) was normalised (less than 107 mmHg) from 3 to 7 h and was still below predose level 23 h after ingestion. The only reported side effects were postural dizziness in 2 cases (corresponding to a fall in systolic upright blood pressure to less than 95 mmHg) and headache in one case. A biphasic variation in heart rate and plasma renin activity, with an early drop and a subsequent tendency to a slight rise, was observed after an intermediate or high dose of prizidilol. Plasma norepinephrine levels were increased by a high dose of prizidilol, while plasma epinephrine, aldosterone and plasma and urinary electrolytes were not consistently changed. Prizidilol in a a single oral dose appeared to be a potent antihypertensive agent. The profile of heart rate and plasma renin point to early dominance of beta-blockade followed by appearance of the concomitant vasodilator properties of prizidiol.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D012083:Renin / Q000097:blood*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011724:Pyridazines; D014665:Vasodilator Agents; D000450:Aldosterone; D012083:Renin; C024293:prizidilol