Non-peptide δ opioid agonists and antagonists (Part II)

A continuing effort in the development of non-peptide delta opioid agonists and antagonists has been seen in the last two years. The first non-peptide delta opioid antagonist naltrindole has represented for years the starting point for the design of novel potent and selective delta opioid ligands. Several research groups are still working on the framework of this prototype and have produced a large number of new derivatives with different in vitro and in vivo pharmacological activities. The discovery of TAN-67, BW373U86 and SNC 80 stimulated other lines of research aimed at synthesising analogues with better delta opioid agonist profile and suitable in vivo activity. Chemically unrelated compounds have also been disclosed deriving from the structural comparison of previously identified ligands. These studies have given further insights about the key determinants for the selective interaction with the delta opioid receptor (DOR). The availability of these tool compounds has allowed significant progression in the understanding of the pharmacology associated with the DOR. In addition to the possible use of selective delta opioid agonists as safe and effective pain relief agents, other interesting activities of possible clinical interest have been disclosed e.g., antiviral, cardioprotective and diuretic activity. Furthermore, many scientific reports confirmed the interesting pharmacological activities associated to the selective blockade of the DOR with antagonists e.g., immunosuppression and prevention of substance abuse. This review will focus on the above research activities, highlighting the most relevant literature and patent reports of the last two years. The medicinal chemistry and the competitive scenario related to non-peptide delta opioid ligands will be considered. Emphasis on the therapeutic potential of selective delta opioid ligands will also be discussed throughout the present review.