Non-peptide delta 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. S everal research groups are still working on the framework of this prototype and have produced a large number of new derivatives with different in vitr o and in vivo pharmacological activities. The discovery of TAN-67, BW373U86 and SNC 80 stimulated other lines of research aimed at synthesising analog ues 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 interac tion with the delta opioid receptor (DOR). The availability of these tool c ompounds has allowed significant progression in the understanding of the ph armacology associated with the DOR. In addition to the possible use of sele ctive 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 s cientific reports confirmed the interesting pharmacological activities asso ciated to the selective blockade of the DOR with antagonists e.g., immunosu ppression and prevention of substance abuse. This review will focus on the above research activities, highlighting the most relevant literature and pa tent reports of the last two years. The medicinal chemistry and the competi tive scenario related to non-peptide delta opioid ligands will be considere d. Emphasis on the therapeutic potential of selective delta opioid ligands will also be discussed throughout the present review.