Effects of 5 derivatives of 3-azabicyclo 3,3,1.nonanes on isolated guinea pig ileum myenteric plexus-longitudinal muscle

Five derivatives of 3-azabicyclo [3,3,1] nonanes all inhibited the contaction of guinea pig ileum myenteric plexus-longitudinal muscle(GPIML)induced by electrical stimulation.Except P7520, the inhibitions of all compounds were more potent than that of morphine. The relatively specific mu receptor antagonist naloxone completely reversed their inhibitory effects.The concentration-response curves of these compounds were parallel to that of morphine. There were good correlations between inhibitory potencies on GPIML and analgesic potencies in mouse hot plate test, mouse writhing test and rat tail-flick test,and binding affinities for the opiate receptors of mouse brain for these 5 compounds. These results supported the view that the analgesic actions of these compounds were mainly related to mu receptors. The inhibitory potency of P7521(IC50 85 pM)on GPIML was 4134 times that of morphine(IC50 0.35 microM), indicating that P7521 had a high affinity for mu receptors in GPIML.