Opiate receptors, endorphins and drug therapy

A number of opioid peptides isolated from brain and peripheral tissue have been identified, and several types of opiate receptor postulated for these endogenous substances. In this study the effects of pharmacological manipulation of 5-hydroxytryptamine (5-HT) on the antinociceptive activity of morphine and two synthetic enkephalin analogus (D-ala2-leu-enkephalin and D-ala2-met-enkephalin) were investigated in mice and rats. Centrally injected 5-HT and peripheral clomipramine pretreatment potentiated both morphine and synthetic enkephalin analgesia whilst peripheral doses of cyproheptidine, lesions in the dorsal medial raphe (DMR) and reserpine pretreatment attenuated opioid analgesia. In the reserpine-pretreated group, centrally injected 5-HT restored the antinociceptive activity of morphine and D-ala2-leu-enkephalin. These results are discussed with respect to clomipramine therapy.