Premium
Partial agonism of cardiac β‐adrenoceptor Blocking Agents and Competitive Conformer‐Receptor Occupancy
Author(s) -
Davies R. H.,
Smith L. H.
Publication year - 2009
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560180732
Subject(s) - agonist , conformational isomerism , competitive antagonist , partial agonist , chemistry , antagonist , receptor , stereochemistry , agonism , biochemistry , molecule , organic chemistry , politics , political science , law
The possibility that different conformations of a drug may control agonist and antagonist action upon biological receptors is explored in terms of a competitive conformer‐receptor occupancy model. Partial agonism is shown to be a function of four parameters, the binding constants of the agonist and antagonist conformers, and the relative populations of the conformers. The relation to Michaelis‐Menten formalism is defined. Application of the model to the partial agonist activity of phenoxypropanolamines on cardiac β‐adrenoceptors suggests that a similar conformation of the compounds controls both agonist and antagonist action on the receptor, but the agonist conformation has a marked additional conformational restriction and a displacement within the receptor to initiate a stimulatory response.