Relationship between hydrophobicity and beta-blocking potencies, affinities or dissociation of beta-blockers from beta-adrenoceptors.
The present study was performed to assess the relationship between the hydrophobicity of drugs and (1) inhibitory strength (pA2) on chronotropic or inotropic actions, (2) displacemental potencies of 3H-CGP12177 or 125I-iodocyanopindolol binding to beta-adrenoceptors (beta-ARs) (pKi) or (3) dissociating potencies of these drugs from beta-ARs of atria strips pretreated with drugs. The beta-blockers used in the present study were bopindolol, active metabolite of bopindolol (18-502), atenolol, propranolol, pindolol, nadolol, alprenolol, oxprenolol, metoprolol, labetalol and acebutolol. The value of the partition coefficient of propranolol was the highest, and that of the beta1-selective blocker atenolol was the lowest. Although low correlation coefficients between hydrophobicity and inhibitory beta-blocking potencies determined by pharmacological experiments or displacemental potencies by the radioligand binding assay using 3H-CGP12177 and 125I-iodocyanopindolol were observed, significant relationships between hydrophobicities of these drugs and dissociating potencies from beta-ARs were observed. These results suggest that the hydrophobicity of drugs may be important for the slow dissociation from beta-ARs, but not for the beta-blocking action.
Nakamura
T
T
Department of Pharmacology, Niigata College of Pharmacy, Japan.
Hosohata
Y
Y
Hosohata
K
K
Hattori
K
K
Suzuki
J
J
Nagatomo
T
T
D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D066298:In Vitro Techniques; D020120:Iodocyanopindolol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; C033394:CGP 12177