Objective

In preclinical studies, activation of delta opioid receptors (DOR) provides poor relief from acute pain but, remarkably, a variety of agonists have been demonstrated to be very effective analgesics in chronic pain models. Some have also shown antidepressant/anxiolytic-like activity which would be a valuable clinical property in chronic pain patients. Such agonists have none of the unwanted side effects (respiratory depression, constipation etc.) associated with conventional mu opioid receptor-activating drugs. Despite their clear potential as chronic pain medicines, very few DOR agonists have even reached clinical trial and, in this presentation, the reasons behind this failure will be discussed. Some early DOR agonists had pro-convulsant activity and this became recognised as a class property. However, more recently produced compounds do not share this side effect which appears to be structurally rather than target-related. An emerging strategy is to develop DOR agonists that signal in a biased fashion and, in this presentation, an example of this approach will be discussed in the description of PharmNovo’s candidate compound PN6047.