Studies on concurrent alpha- and beta-adrenoceptor blocking action of S-596 (arotinolol).

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Abstract
The effects of a therapeutic dose of oral S-596 upon the cardiovascular response to i.v. isoproterenol and noradrenaline were studied in 2 hypertensive and 4 normotensive [human] subjects 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, i.v. isoproterenol increased both heart rate and pulse pressure in a dose-dependent manner. Similarly, i.v. noradrenaline [norepinephrine] 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.

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