Interaction of morphine-epoxide with multiple opiate receptors.

We examined the interaction of morphine-epoxide, which was assumed to be a new metabolite of morphine, with opiate receptor subtypes using pharmacological and biochemical techniques. Morphine-epoxide was about 3 to 4 times less potent than morphine to the interactions of opiate receptors. However, the ratio of IC50 values for the guinea pig ileum and mouse vas deferens to electrical field stimulation and the ratio of IC50 values for the [3H]-dihydromorphine and [3H]-D-ala2-D-leu5 enkephalin binding to rat brain membrane preparations of morphine-epoxide was similar to those of morphine. Morphine-epoxide had virtually no effect on the twitch responses of rabbit and rat vas deferens. Furthermore, "sodium ratio" and "GTP ratio" of morphine-epoxide were similar to those of morphine and differed from naloxone. These results suggest that morphine-epoxide as well as morphine behaves as the agonist on the mu type opiate receptor notwithstanding that the affinity of morphine-epoxide is slightly less than that of morphine.