Relation of Structure of Synthetic Muscarines and Muscarones to Their Pharmacological Action.

Abstract

Comparison of the potency of muscarine and synthetic congeners on smooth muscle (rabbit gut, dog bladder and mouse iris) and on skeletal muscle (frog rectus abdominis) demonstrated equal potency of synthetic and natural L-(+) muscarine. The potency of muscarine is stereospecific; D-(-) muscarine and all racemic stereoisomers (epi, allo, epiallo) possess only a fraction of the potency of dl-muscarine. Keto analogs of muscarines (muscarones) are more potent than muscarine in stimulating smooth muscle; in addition, they possess, on frog skeletal muscle, remarkable nicotinic activity of which the muscarines are almost devoid. The potency of muscarones is not stereospecific. Both + and - muscarones are more potent than L-(+) muscarine, and dl-allo muscarone is only slightly less potent than dl-muscarone.