Anticholinergic activity in mice and receptor-binding properties in rats of a series of synthetic tropane derivatives

A tropane ester, three tropane ethers, atropine and mecamylamine were compared in mice for their antimuscarinic and anti-nicotinic activity against arecoline-induced tremor and nicotine-induced convulsions, respectively. Their receptor-binding characteristics were studied in neuronal membranes prepared from rat cerebral cortex. The results showed that the tropane ester, 2 alpha R-tropanyl benzylate, was more potent than atropine in its antimuscarinic activity, but the anti-muscarinic activity of the tropane ethers, 2 alpha-(2',2'-diphenyl-2'-hydroxyethoxy)tropane (alpha-DPT) and its two isomers (1R,2 alpha R- and 1S,2 alpha S-) were less potent than that of atropine. In contrast with their anti-muscarinic potency, 2 alpha R-tropanyl benzylate and the three tropane ethers were equipotent in their anti-nicotinic activities. The order of potencies of these compounds to displace the binding of [H-3]quinuclidinyl benzylate to brain membranes was similar to that of their anti-muscarinic potencies. The binding of [H-3]nicotine to nicotinic receptors from brain was not inhibited by these compounds. Analyses of structure-activity relationships of these compounds suggested that it is the ester groups that determine the anti-muscarinic potencies of 2 alpha R-tropanyl benzylate; their anti-nicotinic activities were independent of the structural changes and of the anti-muscarinic activities of these compounds.