Studies on concurrent alpha- and beta-adrenoceptor blocking action of S-596 (arotinolol).
The effects of a therapeutic dose of oral S-596 upon the cardiovascular response to intravenous isoproterenol and noradrenaline were studied in 2 hypertensive and 4 normotensive subjects in order to evaluate the drug's mode of action. After oral administration of S-596, mean blood pressure rose slightly and the heart rate decreased. In addition, cardiac output decreased considerably and total peripheral resistance increased. However pulmonary arterial end-diastolic pressure and right atrial pressure were not affected by S-596 administration. Before S-596, intravenous isoproterenol increased both heart rate and pulse pressure in a dose-dependent manner. Similarly, intravenous noradrenaline increased both systolic and diastolic pressures. Following 15 mg of S-596, the effects of isoproterenol were antagonized such that the cumulative log-dose-response curves of the mean isoproterenol-induced increases in heart rate and reductions in diastolic pressure were shifted in parallel to the right. At the same time, the mean noradrenaline-induced increases in blood pressure were also antagonized in a competitive manner. The mean ratio of alpha- and beta-components was calculated as: (formula: see text) From this result it can be suggested that the alpha-adrenoceptor blockade potency of this drug is approximately one-eight of its beta-adrenoceptor blockade potency.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C024523:arotinolol; D007545:Isoproterenol; D009638:Norepinephrine