Cardiac electrophysiologic actions of SCH 19927 (Dilevalol), the R,R- isomer of labetalol

JJ Lynch, DG Montgomery and BR Lucchesi

The cardiac electrophysiologic, hypotensive and antiadrenergic actions of SCH 19927, the R,R-isomer of labetalol, were evaluated in urethane- anesthetized dogs. The cumulative administration of 0.3, 1.0 and 3.0 mg/kg i.v. decreased mean arterial pressure by 18 to 26 mm Hg from a pretreatment value of 106 +/- 6 mm Hg and slightly enhanced atrioventricular nodal conduction. After 3.0 mg/kg of SCH 19927, sinoatrial (SA) conduction times were decreased, whereas intraventricular conduction was depressed slightly. SCH 19927, 10.0 mg/kg, reduced mean arterial pressure by 39 mm Hg and enhanced SA nodal conduction and recovery after overdrive pacing (decreased SA conduction time and corrected sinus node recovery times), whereas intraventricular conduction times and the rate-corrected QTc interval were prolonged. Sinus heart rate, atrial, ventricular and atrioventricular nodal functional and effective refractory periods were unaltered by SCH 19927, 0.3 to 10.0 mg/kg. The administration of SCH 19927 produced significant beta adrenergic receptor blockade, as determined by inhibition of the positive chronotropic and peripheral vasodilatory response to isoproterenol, but did not alter the alpha-1 adrenergic receptor-mediated vasopressor response to phenylephrine. The results indicate that SCH 19927, in beta adrenergic receptor blocking and hypotensive dosages, does not depress SA nodal or atrioventricular nodal function, thus suggesting an electrophysiologic spectrum of activity different from that of other beta adrenergic receptor antagonists.

Volume 239, Issue 3, pp. 719-723, 12/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics