Introduction: The δ opioid receptor mediates various pharmacological effects such as antinociceptive and antidepressant effects, whereas it does not appear to induce μ opioid-like side effects such as dependence, respiratory depression and constipation. Therefore, the δ opioid receptor is a promising drug target.
Areas covered: This review covers literature and patents concerning non-peptidic δ opioid receptor agonists, antagonists, modulators and ligands from 2000 to 2012. Pharmacological effects induced by δ receptor agonists or antagonists are also discussed.
Expert opinion: Potential therapeutic effects by δ receptor agonists are antinociceptive, antidepressant, anxiolytic, cardioprotective and neuroprotective effects. Among them, anxiolytic effects are of particular interest because the anxiolytic effects by a δ receptor agonist have been observed in humans. Although non-peptidic δ receptor agonists were reported to show convulsive effects via the δ opioid receptor, some δ receptor agonists are known to produce no convulsive behaviors. Therefore, it may be possible to eliminate convulsion induced by a δ receptor agonist. Many δ receptor antagonists were also reported but there is little new information about pharmacological effects by a δ receptor antagonist. Although detailed results were not revealed, two δ receptor antagonists with μ receptor agonistic or antagonistic properties are in the late stages of the clinical trial.