The effects of receptor selective opioid peptides on morphine-induced analgesia

Utilizing the mouse tail-flick assay, four opioid peptides, which have been reported to be selective for either μ- or δ-opioid receptors, were examined for their analgesic potency and for their ability to modify morphine-induced analgesia. [D-Ala²,D-Leu⁵]enkephalin and [D-Ser²,Thr⁶]leucine-enkephalin, putative δ-receptor selective peptides, produced a potent analgesic response and at subanalgesic doses potentiated morphine-induced analgesia. Morphiceptin and [D-Ala²,Pro⁵]enkephalinamide, putative μ-receptor selective peptides, were similarly found to produce analgesia. However, in contrast to the δ-receptor selective peptides, three μ-receptor selective peptides were unable to alter the potency of morphine. Thus, it would appear that the potentiation of morphine analgesia is a unique property of δ-receptor selective peptides.