Enkephalins and Endorphins. Clinical, pharmacological and therapeutic implications

During the past 8 years there has been substantial progress in our understanding of the structure, distribution and action of endogenous opioid peptides. Currently, there appear to be 2 groups of peptides; those derived from beta-lipotropin and an enkephalin-related group. Some of these peptides have been shown to be distributed widely in the central nervous system and in endocrine tissues. The activity of the peptides probably occurs at several receptors but only 1 relatively specific (mu-receptor) antagonist, naloxone, is well studies. Although there have been many clinical studies of the action of opioids in man, no novel therapeutic applications have yet been established in clinical practice. Of the many areas of involvement attributed to opioids, those of analgesia, reproductive endocrinology, opiate dependence, and certain as yet undefined subtypes of major psychoses seem reasonably promising. Speculation surround opioid involvement in other disorders such as spinal trauma, septic shock, alcohol dependence, "functional' gastrointestinal disease, diabetes and asthma is of considerable interest but is supported by less clinical evidence. It seems that as research in opioids advances, the putative physiological opioid "spheres of influence' widen. At the same time, opioid mechanisms of action are being revealed to be more subtle and complex than previously thought. As a consequence, the expectations of rapid therapeutic application of opioid peptides and their antagonists are being modified and refined and realistic research strategies applied. In view of the work reviewed in this paper it seems reasonable to expect that such work will pay dividends in the not too distant future.