Title:δ Opioid Receptor Inverse Agonists and their In Vivo Pharmacological Effects
Volume: 20
Issue: 31
Author(s): Shigeto Hirayama and Hideaki Fujii*
Affiliation:
- Laboratory of Medicinal Chemistry and Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5- 9-1, Shirokane, Minato-ku, Tokyo 108-8641,Japan
Keywords:
δ Opioid receptor, Constitutive activity, Inverse agonist, Neutral antagonist, Anorectic effect, Short-term memory
improving effect, Antitussive effect.
Abstract: The discovery of δ opioid receptor inverse agonist activity induced by ICI-174,864, which
was previously reported as an δ opioid receptor antagonist, opened the door for the investigation of
inverse agonism/constitutive activity of the receptors. Various peptidic or non-peptidic δ 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 δ opioid receptor inverse agonist.
After the observation of anorectic effects with the δ opioid receptor antagonism was discussed in
the early 2000s, the short-term memory improving effects and antitussive effects have been very recently
reported as possible pharmacological effects induced by a δ opioid receptor inverse agonist. In
this review, we will survey the developed δ opioid receptor inverse agonists and summarize the possible
in vivo pharmacological effects by δ opioid receptor inverse agonists. Moreover, we will discuss
important issues involved in the investigation of the in vivo pharmacological effects produced by a δ
opioid receptor inverse agonist.
