An analysis of the beta 2-adrenoceptor selectivity in three series of beta-adrenoceptor agonists.
The aim of the study was to analyse the beta 2-adrenoceptor selectivity earlier found in two series of catecholamines and one series of resorcinolamines (Johansson et al. 1986). The affinity of the compounds was assessed in binding studies in preparations from the guinea-pig left heart ventricle (beta 1-adrenoceptors) and the soleus muscle (beta 2-adrenoceptors) using 3H-CGP-12177 as radioligand. Further, the activation of the adenylate cyclase by the compounds was studied in the same preparations. Selectivity quotients were obtained from both functional effects and from affinity and adenylate cyclase activating studies. There was a good correlation between the selectivity quotients obtained in these two ways. Tertiary butyl substitution on the amino nitrogen gave the highest beta 2-adrenoceptor selectivity in both the catechol and resorcinol series. In comparison with their isopropyl substituted analogues the beta 2-adrenoceptor selectivity of these compounds (KWD 2026 and terbutaline) was mainly due to a change in affinity for the beta 1- and beta 2-adrenoceptors and, to a lesser degree, a change in intrinsic efficacy.
Johansson
L H
LH
Research and Development Department, AB Draco, Lund, Sweden.
Eliasson
E L
EL
Persson
H
H
Rosengren
E
E
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002396:Catechols / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008771:Nordefrin / Q000031:analogs & derivatives / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012118:Resorcinols / Q000494:pharmacology; D013726:Terbutaline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D002396:Catechols; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D012118:Resorcinols; C011595:colterol; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D013726:Terbutaline; D008771:Nordefrin; C033394:CGP 12177