Opioid mechanisms and opioid drugs

Opioid analgesic drugs mimic the actions of three groups of endogenous opioid peptides, the enkephalins, dynorphins and endorphins. Opioid receptors have been cloned and have been classified as OP1 (delta), OP2 (kappa), OP3 (mu) and OP4 (ORL-1). The first three correspond to the classical opioid receptors that mediate analgesia. The fourth has a hyperalgesic effect and its natural ligand, nociceptin, lacks the tyrosine molecule common to the analgesic opioid peptides. Opioid receptors are found in several sites in the pain pathways. Drugs with selectivity for one of the opioid receptors have not, as yet, yielded the ideal analgesic, as many of the adverse effects of opioid drugs are mediated by the same receptor that produces analgesia (the OP3 or mu receptor). Selective agonists at non-mu sub-types of opioid receptors do not exert useful global analgesic properties. Their clinical use may be limited to specific pathologies where pain relief is just one component of their beneficial action.