Comparison of interactions of R(+)- and S(-)-isomers of beta-adrenergic partial agonists, befunolol and carteolol, with high affinity site of beta-adrenoceptors in the microsomal fractions from guinea-pig ciliary body, right atria and trachea.
1. The stereoselectivities of beta-adrenergic partial agonists for the high affinity binding site of beta-adrenoceptors in the guinea-pig ciliary body, right atria and trachea were studied. 2. The inhibition curves by the S(-)-isomers of befunolol and carteolol were not significantly different from that by the R(+)-isomers in the guinea-pig ciliary body. 3. The inhibition curves by the S(-)-isomers of befunolol and carteolol were about 10 times as potent as the R(+)-isomers in the guinea-pig atria and trachea. 4. The pKi values of the S(-)-isomers of befunolol and carteolol were significantly larger than those of R(+)-isomers in the guinea-pig atria and trachea but not larger than those of the R(+)-isomers in the guinea-pig ciliary body. 5. These results suggest that the high affinity binding site of beta-adrenoceptors in ciliary body cannot discriminate stereoselectively between the R(+)- and S(-)-isomers, while in other tissues there is stereoselectivity between the two enantiomers.
Koike
K
K
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Horinouchi
T
T
Takayanagi
I
I
D000318:Adrenergic beta-Agonists / Q000378:metabolism* / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002354:Carteolol / Q000378:metabolism* / Q000494:pharmacology*; D002924:Ciliary Body / Q000196:embryology* / Q000648:ultrastructure*; D006168:Guinea Pigs; D006325:Heart Atria / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000378:metabolism* / Q000648:ultrastructure*; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure*; D011412:Propanolamines / Q000378:metabolism* / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism*; D013237:Stereoisomerism; D014132:Trachea / Q000378:metabolism* / Q000648:ultrastructure*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C006034:befunolol; D002354:Carteolol