Da Re P, Valenti P, Fabbri G, Frigeni V, Reggiani A, Della Bella D
Department of Pharmaceutical Sciences, University of Bologna, Italy.
Drugs Exp Clin Res. 1988;14(11):687-92.
A number of symmetrical as well as asymmetrical bis-arenoxypropanolamines have been synthesized and evaluated for their beta-adrenolytic properties. The pharmacological characterization of these compounds was performed in vitro by direct studies (3H-dihydroalprenolol was used as the specific ligand for beta-receptors), and by determining the beta-blocking capacity on isoproterenol (ISO)-induced increased heart rate (isolated guinea-pig atrium); and in vivo by evaluating the antagonism on ISO-induced hypotension and tachycardia, as well as the intrinsic sympathomimetic activity (ISA) on reserpinized and vagotomized rats. The best result was observed with the simplest derivative, i.e. the bis-phenoxypropanolamine compound, which shows in vitro and in vivo potencies almost comparable to propranolol and, moreover, significant bronchodilating activity.
已合成了多种对称和不对称的双芳氧基丙醇胺，并对其β-肾上腺素能阻断特性进行了评估。这些化合物的药理学特性通过体外直接研究（使用3H-二氢阿普洛尔作为β受体的特异性配体）以及测定对异丙肾上腺素（ISO）诱导的心率增加（离体豚鼠心房）的β阻断能力来进行；在体内则通过评估对ISO诱导的低血压和心动过速的拮抗作用，以及对利血平化和迷走神经切断大鼠的内在拟交感活性（ISA）来进行。在最简单的衍生物即双苯氧基丙醇胺化合物中观察到了最佳结果，该化合物在体外和体内的效力几乎与普萘洛尔相当，而且具有显著的支气管扩张活性。
