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/disordering effects of CH-103, a beta-adrenergic receptor antagonist, were compared 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-phenyl-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 decreased in the same order. CH-103 and propranolol significantly increased the fluidity of the membrane in a concentration-dependent manner, whereas practolol reduced fluidity. These physicochemical parameters correlated with the effects of these drugs on rat sarcolemmal Ca2+, Mg(2+)-ATPase, a manifestation of their nonspecific membrane activity. Our results suggest that the physicochemical properties of CH-103, similarly to those of propranolol, are the main determinants of its nonspecific membrane activity.
Varga
E
E
Department of Pharmacology, University Medical School of Debrecen, Hungary. vargae@king.pharmacol.dote.hu
Szöllösi
J
J
Antal
K
K
Kovács
P
P
Szabó
J Z
JZ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000605:Amino Alcohols / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005454:Fluorescence Polarization; D066298:In Vitro Techniques; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D011217:Practolol / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D012661:Semen / Q000166:cytology / Q000187:drug effects; D013499:Surface Properties; D013500:Surface Tension
D000319:Adrenergic beta-Antagonists; D000605:Amino Alcohols; C014893:naphthoxybutanolcyclohexylamine; D011433:Propranolol; D011217:Practolol