title: Pharmacology of ASL-8052, a novel beta-adrenergic receptor antagonist with an ultrashort duration of action.
abstract: ASL-8052, a novel beta-adrenergic receptor antagonist, was studied in isolated guinea pig cardiac and tracheal tissues, in isolated frog sciatic nerves, and in anesthetized dogs. The compound was a moderately potent beta-adrenoceptor antagonist in right atria (pA2 6.96) but was much less active in tracheal tissues (pA2 5.33), indicating cardioselective properties. ASL-8052 possessed a small degree of intrinsic sympathomimetic action in isolated guinea pig right atria and caused direct cardiac depression only at concentrations 1,000-fold higher than its cardiac pA2. Significant local anesthetic action in frog sciatic nerve occurred at extremely high concentrations of ASL-8052 (greater than 0.1 M). In anesthetized dogs, ASL-8052 produced steady-state levels of beta-blockade within 10 min during a 3-h intravenous infusion. In contrast, propranolol produced increasing levels of blockade throughout most of the infusion period. Recovery from beta-blockade occurred rapidly following termination of ASL-8052 infusion (80% recovery in approximately 12 min), whereas very little recovery occurred following cessation of propranolol infusion. Intravenous infusion of ASL-8052 produced dose-dependent blockade of cardiac responses to isoproterenol but only minimally decreased hindlimb vascular responses to isoproterenol. The results indicate that ASL-8052 is a novel cardioselective beta-blocker with an ultrashort duration of action.
mesh_terms: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000779:Anesthetics, Local; D000818:Animals; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D066298:In Vitro Techniques; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011894:Rana pipiens; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000779:Anesthetics, Local; D011412:Propanolamines; D011433:Propranolol; D008790:Metoprolol; C036604:esmolol