ANALGESIC, ANTIMUSCARINIC ACTIVITY AND ENANTIOSELECTIVITY OF THE 4 ISOMERS OF 3-QUINUCLIDINYL TROPATE AS COMPARED WITH THE ENANTIOMERS OF HYOSCYAMINE

The four stereoisomers of 3-quinuclidinyl tropate (2) were Synthesized and their absolute configuration established. The analgesic activity of the four isomers on the hot-plate test and their muscarinic antagon ism on rabbit vas deferens (M(1)), guinea-pig heart (Force, M(2)) and ileum (M(3)) and on the muscarinic receptors present in immature guine a-pig uterus were evaluated. The results were compared with those of t he enantiomers of hyoscyamine (1). No apparent correlation was found b etween the analgesic activity and antimuscarinic activity on M(1), M(2 ) and M(3) receptors, whereas striking differences exist between the a ffinity values of the analgesic enantiomer of hyoscyamine (R-(+)-1) an d those of the inactive isomers of 2 on the muscarinic receptor presen t in immature guinea pig uterus. Molecular Modelling studies have show n that the only difference between 1 and 2 lies in the volumes occupie d by the basic part of the molecules.