Pharmacology of bevantolol hydrochloride.
Bevantolol is a cardioselective, beta-adrenoreceptor antagonist, devoid of intrinsic beta sympathomimetic activity and with weak membrane-stabilizing and local anesthetic properties. The 3,4-dimethoxyphenylethylamino moiety, substituted on the side chain amine function, confers cardioselectivity, which has been confirmed by a number of experiments. In vitro, bevantolol demonstrated greater antagonism of atrial than tracheal responses to isoproterenol. In vivo, bevantolol preferentially inhibited isoproterenol-induced tachycardias in conscious and anesthetized dogs, compared with the nonselective agent propranolol. Conversely, its effect on blood pressure after isoproterenol was minimal compared with propranolol, reflecting its muted effect on beta 2 peripheral receptors. A functional difference between bevantolol and propranolol was demonstrated in histamine-challenged guinea pigs. Bevantolol had little effect on the antiasthmatic effect of isoproterenol, whereas propranolol blocked it totally. Bevantolol's lack of intrinsic sympathomimetic activity was demonstrated in normal and reserpinized dogs, where it was devoid of intrinsic sympathomimetic activity at doses up to 10 mg/kg. Similarly, intravenous doses of 10 mg/kg had to be administered before direct myocardial depression occurred in the reserpinized animals. Metabolite 3, which is excreted in trace amounts in human urine, demonstrates intrinsic sympathomimetic activity when administered in pharmacologic doses to dogs; however, any clinical relevance remains to be established. Several laboratories have demonstrated that bevantolol interacts at alpha-adrenergic sites. These data require further investigation. The dose-related antihypertensive effect of bevantolol has been demonstrated in spontaneously hypertensive and 2 kidney, 1 clip renal hypertensive rats. Animal experiments also suggest that bevantolol may be useful in angina: It caused a favorable redistribution of blood flow in dogs in which the left circumflex artery had been stenosed.(ABSTRACT TRUNCATED AT 250 WORDS)
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000779:Anesthetics, Local; D000787:Angina Pectoris / Q000188:drug therapy; D000818:Animals; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D055598:Chemical Phenomena; D002621:Chemistry; D006321:Heart / Q000187:drug effects; D009928:Organ Specificity; D011412:Propanolamines / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D013566:Sympathomimetics
D000319:Adrenergic beta-Antagonists; D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D013566:Sympathomimetics; C021148:bevantolol