Delta Opioid Receptor Inverse Agonists and Their in vivo Pharmacological Effects.

The discovery of delta opioid receptor inverse agonist activity induced by ICI-174,864, which was previously reported as a delta opioid receptor antagonist, opened the door for the investigation of inverse agonism/constitutive activity of the receptors. Various peptidic or non-peptidic delta opioid receptor inverse agonists have since been developed. Compared with the reports dealing with in vitro inverse agonist activities of novel compounds or known compounds as antagonists, there have been almost no publications describing the in vivo pharmacological effects induced by a delta opioid receptor inverse agonist. After the observation of anorectic effects with the delta opioid receptor antagonism was discussed in early 2000s, the short-term memory improving effects and antitussive effects have been very recently reported as possible pharmacological effects induced by a delta opioid receptor inverse agonist. In this review, we will survey the developed delta opioid receptor inverse agonists and summarize the possible in vivo pharmacological effects by delta opioid receptor inverse agonists. Moreover, we will discuss important issues involved in the investigation of the in vivo pharmacological effects produced by a delta opioid receptor inverse agonist.