Delta opioid agonists: a concise update on potential therapeutic applications.
OBJECTIVE
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.


METHODS
A literature search of the PUBMED database and a combination of keywords including delta opioid receptor, analgesia, mood and individual compounds identified therein, from industry and other source, and from www.clinicaltrials.com.


CONCLUSIONS
DOR agonist and antagonist ligands have been developed with ever increasing affinity and selectivity for DOR over other opioid receptor subtypes and studied for therapeutic utility, primarily for pain relief, but also for other clinical endpoints.


CONCLUSIONS
Selective DOR agonists have been designed with a large increase in therapeutic window for a variety of potential CNS applications including pain, depression, and learning and memory among others.
Center for Bioethics, Pain Management and Medicine, University City, MO, USA; Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA.
J F
JF
Peppin
R B
RB
Raffa
D000928:Antidepressive Agents / Q000494:pharmacology; D004361:Drug Tolerance / Q000502:physiology; D004745:Enkephalins / Q000378:metabolism; D006801:Humans; D007858:Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009293:Opioid-Related Disorders / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology*; D011957:Receptors, Opioid / Q000819:agonists; D017465:Receptors, Opioid, delta / Q000819:agonists*
D000928:Antidepressive Agents; D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta
delta opioid; depression; learning and memory; pain; therapeutic uses