Nonspecific membrane effects of CH-103: hydrophobicity, surface activity and membrane fluidity studies in comparison with propranolol and practolol

The partition coefficient, surface activity and membrane fluidizing/disorde ring effects of CH-103, a beta-adrenergic receptor antagonist, were compare d to those of propranolol and practolol as reference compounds. Changes in membrane fluidity were followed by measuring the steady-state fluorescence anisotropy of bull sperm cells with 1-[4-(trimethylammonium)phenyl]-6-pheny l-1,3,5-hexatriene(TMA-DPH) as a fluorescence probe. The octanol/buffer (pH 7.0) partition coefficients for CH-103, propranolol and practolol were 32. 9, 5.08 and 0.013, respectively; the surface activity of the compounds decr eased in the same order. CH-103 and propranolol significantly increased the fluidity of the membrane in a concentration-dependent manner, whereas prac tolol reduced fluidity. These physicochemical parameters correlated with th e effects of these drugs on rat sarcolemmal Ca2+, Mg(2+)ATPase, a manifesta tion of their nonspecific membrane activity. Our results suggest that the p hysicochemical properties of CH-103, similarly to those of propranolol, are the main determinants of its nonspecific membrane activity.