Bevantolol Hydrochloride — Preclinical Pharmacologic Profile

Abstract

Bevantolol hydrochloride, a beta adrenoceptor antagonist, can be catego rized using conventional schemes as being cardioselective, devoid of intrinsic sympathomimetic activity and having weak membrane-stabilizing and local an esthetic properties. The cardioselectivity of bevantolol was conferred by the incorporation of a 3,4-dimethoxyphenyl moiety into the terminal amino portion of the molecule. This portion of the molecule also appears to account for bevan tolol's in vitro binding affinity at alpha-adrenoceptor sites; the in vivo signifi cance of which remains unclear. In the various cardiovascular disease-state models, bevantolol's profile differed from that of propranolol, i.e., there was no initial pressor response in spontaneously hypertensive or renal hypertensive rats. In a myocardial ischemia model, bevantolol, unlike propranolol, increased contractile function in the ischemic myocardium. A ring hydroxylated urinary metabolite, which occured only in trace amounts in human urine, had an inter esting profile when studied in animals at pharmacologic doses. It ranked high in cardioselectivity (like bevantolol), but unlike bevantolol showed significant in trinsic beta sympathomimetic activity. The clinical significance of this metabo lite, if any, remains to be established. Collectively the preclinical profile of bevantolol showed it to have an interesting profile for a beta adrenoceptor an tagonist in a variety of pharmacologic test systems.