R. Feifel, M. Wagner-Röder, C. Strohmann, Reinhold Tacke, M. Waelbroeck, J. Christophe, E. Mutschler, G. Lambrecht

• 1 Tbc affinities of the (R)- and (S)-enantiomers of hexahydro-difenidol (1) and its acetylenie analogues hexbutinol (2), hexbutinol methiodide (3) and p-fluoro-hexbutinol (4) (stereochemieal purity > 99.8%) for musearlnie receptors in rabbit vas deferens (M1), guinea-pig atria (M2) and guinea-pig ileum (M3) were measured by dose-ratio experiments. 2 The (R)-enantiomers consistently showed higher aßinities than the (S)-isomers. The stereosclectivity ratios [(R)/(S)] wcrc greatest with thc enantiomers of 1 (vas deferens: 550; ilcum: 191; atria:1 Tbc affinities of the (R)- and (S)-enantiomers of hexahydro-difenidol (1) and its acetylenie analogues hexbutinol (2), hexbutinol methiodide (3) and p-fluoro-hexbutinol (4) (stereochemieal purity > 99.8%) for musearlnie receptors in rabbit vas deferens (M1), guinea-pig atria (M2) and guinea-pig ileum (M3) were measured by dose-ratio experiments. 2 The (R)-enantiomers consistently showed higher aßinities than the (S)-isomers. The stereosclectivity ratios [(R)/(S)] wcrc greatest with thc enantiomers of 1 (vas deferens: 550; ilcum: 191; atria: 17) and least with thosc ofthc p-Fluoro-analogue 4 (vas defercns: 34; ileum: 8.5; atria: 1.7). 3 The enantiomerie potency ratios for compounds 1-4 were highest in rabbit vas deferens, intermediate in guinea-pig ileum and much less in guinea-pig atria. Thus, these ratios may serve as a predietor of muscarinic receptor subtype identity. 4 (S)-p-Fluoro-hexbutinol [(S)-4] showed a novel receptor selectivity profile with preference for M\(_3\) receptors: M\(_3\) > M\(_2\) \(\geq\) M\(_1\)• 5 These results do not conform to Pfeiffer's rule that aetivity differences between enantiomers are greater with more potent compounds.…