ALPHA-ADRENOCEPTOR AND BETA-ADRENOCEPTOR BLOCKING PROPERTIES OF LABETALOL AND ITS R,R-ISOMER, SCH-19927

  • 1 January 1981
    • journal article
    • research article
    • Vol. 218  (2) , 435-443
Abstract
Labetalol is a mixture of 4 isomers. Its .alpha.- and .beta.-adrenergic blocking properties were compared to those of the R,R-isomer, SCH 19927. In anesthetized dogs, i.v. administration of both compounds produced competitive .beta.- and .alpha.-blockade as judged by inhibition of the tachycardia and vasopressor responses to i.v. injections of isoproterenol and phenylphrine, respectively. SCH 19927 was 3-4 times as potent a .beta.-blocker, but only 1/3 as potent an .alpha.-blocker as labetalol. The separation of .beta.- and .alpha.-blocking activity of SCH 19927 clearly exceeded that of labetalol. SCH 19927 also demonstrated greater .beta.-blocking potency than labetalol after oral administration to conscious dogs or rats that were subsequently pithed. SCH 19927 did not affect, whereas labetalol slightly reduced, pressor responses to sympathetic stimulation in the pithed rat. Both drugs were relatively devoid of intrinsic .beta.-1 sympathomimetic activity in the ganglion-blocked dog. SCH 19927 is a more potent .beta.-adrenoceptor blocker and less potent .alpha.-blocker than labetalol. The separation of adrenergic blocking activities indicates that steric requirements for .alpha.- and .beta.-blockade differ in the labetalol molecule.