ALLOSTERIC AND COMPETITIVE INTERACTIONS OF -ALPHA-(2',2'-DISUBSTITUTED-HYDROXY-ETHOXY)TROPANE AND ITS OPTICAL ISOMERS AT RAT CENTRAL MUSCARINIC ACETYLCHOLINE-RECEPTORS

Both allosteric and competitive interactions of (alpha)-(2',2'-disubst ituted-hydroxyethoxy)tropane (2(alpha)-DHET) and its four optical isom ers with muscarinic acetylcholine receptors in rat cerebral cortex wer e investigated. 2(alpha)-DHET and its optical isomers allosterically d ecelerated the dissociation of bound [H-3]N-methylscopolamine in a con centration-dependent manner, but these compounds failed to decelerate the dissociation of bound [H-3]quinuclidinyl benzilate. The potencies of 2(alpha)-DHET and its optical isomers to decelerate the dissociatio n of bound [H-3]N-methylscopolamine were not differed significantly, b ut the competitive binding potencies of these compounds were significa ntly different. The order of potencies of 2(alpha)-DHET and its four o ptical isomers to inhibit the binding of [H-3]quinuclidinyl benzilate to central muscarinic acetylcholine receptors was 1S-2(alpha)-2'R>1 2' R>2(alpha)-DHET>1S-2(alpha)-2'S>1R-2(alpha)-2'S, the isomer with 1S-2( alpha)-2'R configuration was about two orders of maginitude more poten t than the isomer with 1R-2(alpha)-2'S configuration. The allosteric p otencies were found not to be correlated with their competitive bindin g potencies.