COMPETITIVE AND ALLOSTERIC BINDING OF 2-ALPHA-DHET AND ITS OPTICAL ISOMERS TO RAT CARDIAC MUSCARINIC RECEPTORS

The possibility of both competitive and allosteric interactions of 2 alpha-(2',2'-disubstituted-hydroxy-ethoxy)tropane (2 alpha-DHET) and its four optical isomers with rat cardiac muscarinic receptors was studied. 2 alpha-DHET and its optical isomers competitively inhibited the binding of [H-3] quinuclidinyl benzilate to rat cardiac muscarinic receptors and allosterically decelerated the dissociation of bound [H-3] quinuclidinyl benzilate in a concentration-dependent manner. The rank order of potencies to displace [H-3] quinuclidinyl benzilate binding was 1R-2 alpha-2'R > 1S-2 alpha-2'R > 2cr-DHET > 1S-2 alpha-2'S > 1R-2 alpha-2'S, while their potencies to decelerate the dissociation of bound [H-3] quinuclidinyl benzilate were not significantly different. The allosteric potencies were found not to be correlated with their binding potencies.