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Delta opioid agonists: a concise update on potential therapeutic applications

The endogenous opioid system co‐evolved with chemical defences, or at times symbiotic relationships, between plants and other autotrophs and heterotrophic predators – thus, it is not surprising that endogenous opioid ligands and exogenous mimetic ligands produce diverse physiological effects. Among the endogenous opioid peptides (endomorphins, enkephalins, dynorphins and nociception/orphanin FQ) derived from the precursors encoded by four genes (PNOC, PENK, PDYN and POMC) are the pentapeptides Met‐enkephalin (Tyr‐Gly‐Gly‐Phe‐Met) and Leu‐enkephalin (Tyr‐Gly‐Gly‐Phe‐Leu). The physiological effects of the enkephalins are mediated via 7‐transmembrane G protein‐coupled receptors, including delta opioid receptor (DOR). We present a concise update on the status of progress and opportunities of this approach.