新しいα，β‐遮断薬，（±）‐４‐〔２‐Ｈｙｄｒｏｘｙ‐３‐（３‐（２‐ｍｅｔｈｏｘｙｐｈｅｎｏｘｙ）‐２‐ｐｒｏｐｙｌａｍｉｎｏ）ｐｒｏｐｏｘｙ〕‐１（２Ｈ）‐ｉｓｏｑｕｉｎｏｌｉｎｏｎｅ（Ｎ‐１５１８）の薬理作用

Abstract

The alpha, beta-adrenergic blocking, antihypertensive and vasodilating properties of N-1518 were compared with those of labetalol. N-1518 blocked alpha- and beta-adrenoceptors competitively as indicated by parallel rightward displacement of the dose-response curve of each agonist in isolated organs and in anesthetized dogs. As judged by pA2 values and DR10 values, N-1518 was as potent as labetalol in blocking alpha- and beta-adrenoceptors. The beta 1/alpha 1 ratio of N-1518 was 8.3 for pA2 values in isolated organs and 13.6 for DR10 values in anesthetized dogs, respectively. N-1518 inhibited dose-dependently the pressor response to intravenous administration of noradrenaline, but labetalol did not depress the response to noradrenaline in anesthetized dogs. N-1518 is composed of four optical isomers. The SR-isomer was the most potent in blocking beta-receptors, and the RR-isomer was the most potent in blocking alpha-receptors. N-1518 has no intrinsic sympathomimetic activity in reserpinized rats and has no local anesthetic activity in guinea pigs. Single oral administration of N-1518 produced a fall in blood pressure in conscious SHR and renal hypertensive dogs without causing tachycardia. Intra-arterially administered N-1518 in the dog hindlimb resulted in vasodilation as indicated by the increase in blood flow. The magnitude of the responses was approximately 3 times more potent than that of labetalol.