Pharmacological activity and receptor-binding characteristics of 2...

This study describes the receptor-binding characteristics, antimuscarinic and antinicotinic activities of 2 beta-(2'-phenyl-2'-cyclopentyl-2'-hydroxy-ethoxy)tropane (beta-PCT) and its four optical isomers. Both arecoline-induced tremor and nicotine-induced convulsion in mice were antagonized by beta-PCT and its optical isomers. These compounds were less potent than atropine in their antimuscarinic potencies, but more potent than atropine in their antinicotinic activities. The isomer with the 1S-2 beta-2'R configuration was about one order of magnitude more potent than the isomer with the 1R-2 beta-2'S configuration in their antimuscarinic activity, but the antinicotinic potencies of these compounds did not differ significantly. The order of potencies of beta-PCT and its optical isomers to displace the specific binding of [3H]quinuclidinyl benzilate to muscarinic receptors was similar to that of their antimuscarinic potencies. The binding of [3H]nicotine to central nicotinic receptors was not inhibited by these compounds. The findings indicate that beta-PCT and its optical isomers are useful affinity ligands to examine the biochemical and functional characteristics of brain cholinergic receptors.