Autoradiography of [3H]ohmefentanyl binding with opiate receptors in rat brain

The opiate receptor localization of [3H]ohmefentanyl, a potent analgesic agent, was studied by autoradiography in rat brain and compared with that of [3H]dihydromorphine (mu) and [3H](D-Ala2, D-Leu5) enkephalin (delta). [3H]Ohmefentanyl was concentrated in various areas of rat brain, the highest densities were found in nuclei caudatus-putamen (streaks and clusters), nuclei habenula, nuclei accumbens, nuclei amygdalae and dorsal horn of spinal cord. High densitites were in thalamus nuclei, inferior colliculus, hippocampus (CA2 stratum pyramidale), frontal cortex (layer I), superior colliculus. These results were similar to the distribution of [3H]DHM. [3H]DADLE-binding sites were in nuclei caudatus-putamen (diffuse), nuclei accumbens and the external plexiform layer of the olfactory bulb. 3-Methyl-fentanyl derivatives competed with [3H]DHM for binding with opiate receptors and reduced the grain counting in nuclei caudatus-putamen and hippocampus (stratum pyramidale), their competitive potencies were correlative with the analgesic effects. It suggests that the analgesic effect of 3-methyl-fentanyl derivatives closely correlates its affinity to opiate receptors. The inhibiting potency of ohmefentanyl for binding of [3H]DHM with opiate receptors in rat brain section was 159 times higher than that of [3H]DADLE, thus indicating that ohmefentanyl possessed high-affinities for mu-opiate receptors.