D. Manetti et al., REDUCED FLEXIBILITY ANALOGS OF ANALGESIC AND COGNITION-ENHANCING ALPHA-TROPANYL ESTERS, Archiv der pharmazie, 329(2), 1996, pp. 105-111
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.