Comparative studies on beta-adrenolytic potencies of some new phenoxyaminopropanol derivatives and celiprolol.
The influence of different substitutions in 4-position of the phenyl ring of three recently developed l-alkylamino-3-phenoxy-2-propanol derivatives on the beta-adrenolytic potency and tissue specificity has been investigated and compared to the cardioselective beta-adrenoceptor antagonist celiprolol. The pA2 values against the isoprenaline tachycardia in isolated right atria (beta 1) and the relaxation of tracheal muscle (beta 2) both of guinea-pigs were expressed as beta 1/beta 2 selectivity ratio. The efficiencies and cardioselectivity of 4-propoxycarbonylderivative (BL 345 Ac) as well as celiprolol were similar, whereas 4-propoxymetylsubstitution (FoA 34t) decreased the inhibiting potency to the heart tissue nearly three times. The elimination of the 4-substitutent leads to the total loss of cardioselectivity (FoA 04). In addition, the character of the 4-substition has also influenced the nonspecific membrane activity expressed as local anesthetic efficiency in experiments on rabbit eyes and guinea-pig skin.
Mlynárová
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Department of Pharmacology and Toxicology, Pharmaceutical Faculty, Comenius University, Bratislava, Slovak Republic.
Racanská
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D000433:1-Propanol / Q000138:chemical synthesis* / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D017272:Celiprolol / Q000494:pharmacology*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011817:Rabbits; D014132:Trachea / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000779:Anesthetics, Local; D000433:1-Propanol; D017272:Celiprolol; D007545:Isoproterenol