Abstract
On guinea pig ileum R-(-)-3-acetoxyquinuclidine is less than one-tenth as active as the S-(+) enantiomer, but the methiodide of the R compound is about 40 times as active as its S enantiomer. Inversion of stereospecificity occurs because methylation reduces the activity of the stronger (S) base about 1000-fold whereas it reduces the activity of the weaker (R) base only about 2-fold. The affinity of the S base is reduced about 100-fold, and this marked effect of methylation may be associated with the rigidity of the quinuclidine ring and indicate a particularly close fit between S-(+)-3-acetoxyquinuclidine and the "muscarinic" receptor. On the frog rectus there is no detectable stereospecificity and activity is not reduced by methylation, but the compounds are not very active.
- Copyright ©, 1975, by Academic Press, Inc.
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