Relationship between analgesic activity and opiate receptor binding affinity of 5 derivatives of 3-aza-bicyclo(3,3,1)nonanes

By means of mouse hot plate test, writhing test and rat tail-flick test; highpressure liquid chromatography and receptorbinding assay, the results are as follows: 1) 5 derivatives of 3-azabicyclo [3,3,1] nonanes showed potent analgesic acticities. 2) Their partition coefficients were>3. 3) 5 derivatives possessed higher binding affinities for opiate receptors in mice brain. 4) There was a good correlation between the analgesic activities and the potencies to inhibit the binding of μ-receptor specific [3H] ligands to opiate receptors for 5 derivatives. However, the analgesic activities of 5 derivatives did not correlate with their partition coefficients. From the abovementioned results, it is concluded that the analgesic actibities of 5 derivatives to opiate receptors and their analgesia is mainly related to μ receptor. In addition, sodium response ratio, GTP response ratio and GTP+NaCl response ratio suggest that P7542, P 7542, P 7522 and P7534 are opioid agonists, but P 7521 and P7520 may be mixed agonist-antagonists.