REDUCED FLEXIBILITY ANALOGS OF ANALGESIC AND COGNITION-ENHANCING ALPHA-TROPANYL ESTERS

A series of semirigid analogs of compounds 1 and 2, two potent analges ics and cognition enhancers, have been synthesized and tested for anti nociceptive activity (hot plate test) and for muscarinic affinity (bin ding in rat cerebral cortex). They were found to be in general less po tent than the reference compounds; only one of them (22) shows a good affinity for the muscarinin receptor and and antinociceptive efficacy comparable with those of the reference compounds. At a dose of 30 mg/k g 22 is also able to reverse the amnesic effect of dicyclomine. Since the analgesic effect of these compounds is affected by the 5-HT4 antag onist SDZ 205557, the possible role of this receptor is discussed.