Comparative findings on the stereoselectivity of cholinoreceptors

The potency of the optical isomers of the muscarinomimetic agent 2-methyl-4-dimethylaminomethyl-1.3-dioxolane methiodide (F-2268) was compared on cholinoreceptors, (ChR) of different animals. The greatest difference between optical isomers was observed on the muscarinic ChR of guinea pig ileum smooth muscle cis-L(+)isomer being more than hundred times as potent as cis-D(-)isomer. On the ChR of muscarinic type in the holothuria Cucumaria japonica retractor muscle, cis-L(+)isomer was 25 times as efficient as cis-D(-)isomer. On the ChR of sea urchin and sipunculid locomotor muscles, optical isomers differ only 3 to 5 times. There was no difference between the effect of optical isomers on the ChR of muscarinic type which mediate hyperpolarization in the neurones of the gastropod mollusc Planorbarius corneus. This suggest that some changes in ChR stereoselectivity may occur in the course of evolution.