Synthesis and pharmacological characterization of new chiral derivatives of muscarine and allo-muscarine

Novel derivatives of natural muscarine and allo-muscarine, i.e. the benzyl ethers (-)-10 and (-)-12 and the benzoate (-)-13, were synthesized in very high enantiomeric excess. Target compounds were tested in vitro on guinea p ig tissues, and their muscarinic potency was evaluated at M-2 (heart force and rate) and M-3 (ileum and bladder) receptor subtypes. The derivatives un der study were also assayed in vive on pithed rat. In addition, muscarinic receptor heterogeneity was investigated by determining the affinity and the relative efficacy of compounds (-)-10, (-)-12 and (-)-13 at M-2 (heart for ce and rate) and M-3 (ileum and bladder) receptor subtypes. (C) 2000 Elsevi er Science S.A. All rights reserved.