The American Autoimmune Related Disease Association lists over 50 different autoimmune diseases. Some of these are common such as multiple sclerosis, type 1 diabetes, Crohns disease and rheumatoid arthritis; some are very rare such as Stiff-man syndrome. One factor that links many of these diseases is an inappropriate proliferation of T cell clones that are reactive to proteins which are important for normal function. Consequently one approach to autoimmune disease has been the identification of immunosuppressants however this class of drugs is traditionally associated with serious side-effects. Thus the search for novel therapies continues. 

A few years ago it was reported for the first time that the delta opioid receptor antagonist, naltrindole was able to reduce T cell proliferation and furthermore this class of drug is able to prolong allograft survival. The development of novel delta opioid receptor antagonists has however been slow. 

Recent data published by University of Innsbruck researchers is therefore particularly exciting. This group have characterized, HS 378 a recently developed indolomorphinan with high selectivity and antagonist potency at the delta-opioid receptor. HS 378 showed 4.7- and 2.4-fold higher mu/delta selectivity compared to naltrindole and naltriben, reference delta antagonists. In a [35S]GTPgammaS functional assay carried out in cell lines expressing cloned human opioid receptors, HS 378 was found to be a pure delta-opioid receptor antagonist. In vitro, exposure of HS 378 resulted in an apparent dose-related suppression of concanavalin A induced rat T-lymphocyte proliferation with an IC50 value of 0.54 microM. The potency of this effect was at least 10-fold greater than references. Given this data, HS 378 has properties that may be of therapeutic value in the setting of human inflammatory diseases and further studies are eagerly awaited in disease models.