Selectivity of bunitrolol for beta 1- and beta 2-adrenergic receptors and 5HT1B-receptors: assessment by biphasic Scatchard plots and biphasic displacement curve analysis with 125I-iodocyanopindolol and 3H-CGP12177.
The preference by bunitrolol for beta 1- and beta 2-adrenoceptors of the rat brain, heart and/or lung was assessed by the radioligand binding assay method with 125I-iodocyanopindolol (125I-ICYP) or 3H-CGP12177. Scatchard plots of 125I-ICYP binding in the presence of bunitrolol were found to be non-linear. The inhibition constants (Ki) of bunitrolol for high (beta 2-) and low affinity sites (beta 1-) were: 0.42 +/- 0.16 nM for beta 1 and 3.55 +/- 1.61 nM for beta 2 (beta 1 greater than beta 2), respectively. Displacement experiments conducted with the preparations of the rat brain using 125I-ICYP or with the preparations of the rat heart using 3H-CGP12177 yielded Ki values for bunitrolol of 0.53 +/- 0.20 (beta 1) and 2.37 +/- 0.78 (beta 2) nM for 125I-ICYP binding and 2.01 +/- 0.38 (beta 1) and 12.67 +/- 6.54 (beta 2) nM for 3H-CGP12177 binding. In addition, the Ki value for 5HT1B-receptors assessed in displacement experiments conducted with 125I-ICYP in the presence of 30 microM I-metoprolol in the rat brain was 10.54 +/- 5.92 nM. Thus, bunitrolol is a beta 1-selective antagonist.
Tsuchihashi
H
H
Department of Pharmacology, Niigata College of Pharmacy, Japan.
Nagotomo
T
T
Imai
S
S
D000319:Adrenergic beta-Antagonists; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives*; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D007457:Iodine Radioisotopes; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D020120:Iodocyanopindolol; D010869:Pindolol; C033394:CGP 12177