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.