The alpha- and beta-adrenoceptor blocking potencies of labetalol and its individual stereoisomers in anaesthetized dogs and in isolated tissues.
1 The antagonist potencies of labetalol and each of its four stereoisomers have been compared at alpha 1-, beta 1- and beta 2-adrenoceptors in anaesthetized dogs and in isolated tissues. 2 The RR stereoisomer is a potent, non-selective antagonist at beta-adrenoceptors but has only weak alpha 1-adrenoceptor blocking activity. 3 The SR stereoisomer was the most potent antagonist at alpha 1-adrenoceptors, and it also had similar potency as an antagonist at beta-adrenoceptors. 4 The alpha- and beta-adrenoceptor blocking profile of the RS stereoisomer is intermediate between that of the RR and SR, but the SS stereoisomer is a relatively weak antagonist at both alpha- and beta-adrenoceptors. 5 It is concluded that, although most of the alpha 1-adrenoceptor blocking activity of labetalol is attributable to the SR stereoisomer and nearly all of its beta-adrenoceptor blocking activity resides in the RR stereoisomer, each of the stereoisomers contributes to the overall pharmacological profile of labetalol.
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000758:Anesthesia; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004285:Dogs; D004983:Ethanolamines / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007741:Labetalol / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013237:Stereoisomerism
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D007741:Labetalol