|Opioid receptor, delta 1|
Structure of the human delta-type opioid receptor with bound Naltrindole. PDB entry
|External IDs||IUPHAR: ChEMBL: GeneCards:|
|RNA expression pattern|
Activation of δ receptors produces some analgesia, although less than that of mu-opioid agonists. Many δ agonists may also cause seizures at high doses, although not all δ agonists produce this effect.
Evidence for whether δ agonists produce respiratory depression is mixed; high doses of the δ agonist peptide DPDPE produced respiratory depression in sheep, but in tests on mice the non-peptide δ agonist SNC-80 produced respiratory depression only at the very high dose of 40 mg/kg. In contrast both the peptide δ agonist Deltorphin II and the non-peptide δ agonist (+)-BW373U86 actually stimulated respiratory function and blocked the respiratory depressant effect of the potent μ-opioid agonist alfentanil, without affecting pain relief. It thus seems likely that while δ opioid agonists can produce respiratory depression at very high doses, at lower doses they have the opposite effect, a fact that may make mixed μ/δ agonists such as DPI-3290 potentially very useful drugs that might be much safer than the μ agonists currently used for pain relief.
Of additional interest is the potential for δ agonists to be developed for use as a novel class of antidepressant drugs, following robust evidence of both antidepressant effects and also upregulation of BDNF production in the brain in animal models of depression. These antidepressant effects have been linked to endogenous opioid peptides acting at δ and μ opioid receptors, and so can also be produced by enkephalinase inhibitors such as RB-101.
Recent work indicates that exogenous ligands that activate the δ receptors mimic the phenomenon known as ischemic preconditioning. Experimentally, if short periods of transient ischemia are induced the downstream tissues are robustly protected if longer-duration interruption of the blood supply is then effected. Opiates and opioids with δ activity mimic this effect. In the rat model, introduction of δ active ligands results in significant cardioprotection.
Until comparatively recently, there were few pharmacological tools for the study of δ receptors. As a consequence, our understanding of their function is much more limited than those of the other opioid receptors for which selective ligands have long been available.
However there are now several selective δ opioid agonists available, including peptides such as DPDPE and deltorphin II, and non-peptide drugs such as SNC-80, the more potent (+)-BW373U86, a newer drug DPI-287, which does not produce the problems with convulsions seen with the earlier agents, and the mixed μ/δ agonist DPI-3290, which is a much more potent analgesic than the more highly selective δ agonists. Selective antagonists for the δ receptor are also available, with the best known being the opiate derivative naltrindole.
Mitragyna speciosa (kratom) indole derivatives:
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- delta Opioid Receptor at the US National Library of Medicine Medical Subject Headings (MeSH)