Analgesic activity and opiate receptor binding of 1-cyclohexyl-4-(1,2-diphenylethyl)piperazine.

It has been stated that there is good correlation between the analgesic activity of narcotic drugs and their inhibitory effects for 3H-naloxone stereospecific binding (1). We reported that R(-)-1,2-diphenyl-l-dimethylaminoethane, (Spa) is the essential structure for morphine like analgesics (2), and that Spa is one-tenth as active as morphine , while the S(+)-enan tiomer is inactive. 1-Cyclohexyl-4-(1,2-diphenylethyl)piperazine was synthesized by modifying the structure of Spa (3, 4). It is interesting that the stereo-activity relationship of this novel narcotic agonist is opposite that of compounds related to morphine (5). Discussed herein are the features of the opiate receptor with respect to the relationship between the receptor binding and the analgesic activity of these optical isomers. Analgesic activities were evaluated in mice by the tail-pinch method (Haffner's method) . All isomers were administered subcutaneously or intraventricularly . Inhibitory effect of those agonists on the stereospecific binding of 5 x 10-9 M 3H-naloxone or 1 x 10-e M 3H morphine to homogenates of rat brain without cerebellum was measured by the filtration method of Pert and Snyder (6). Inhibition of the electrically induced contractions of the longitudinal muscle of the guinea pig ileum by the agonists applied cumulatively was also investigated.