The responses of acetylcholinesterase and conduction in bullfrog sciatic nerve to the stereochemistry of amino alcohol derivatives. III

Abstract

Blockade of the acetylcholinesterase-acetylcholine system and of the conducted impulse in desheathed bullfrog sciatic nerve have been studied with cis-trans isomers of 1,2-diethylaminocyclohexanol, and the phenylacetate, diphenyl acetate, and benzilate esters of the corresponding isomeric dimethyl compounds. The results have been interpreted in terms of possible involvement of the esterase system in the biochemical events connected with propagation of the nerve impulse. It has been found that, in part, a fair degree of parallelism exists in this series between power of a given drug to block the conducted impulse in the nerve, on the one hand, and to inhibit the enzyme system reversibly on the other. However, some interesting anomalies develop in the case of certain diphenyl acetate and benzilate esters treated as cis-trans pairs, in which the power against the nerve is at least a thousandfold greater than might be expected from activity against the isolated enzyme system. In general, it is observed that both the nerve and enzyme are able to differentiate in response to rather subtle spatial variations in the positioning of groups in a given cis-trans pair, but in contrast with the enzyme where each drug acts in a definitely reversible fashion, the nerve shows even greater specificity in the sense that certain of the agents act on it with a fair degree of irreversibility.