ASSOCIATION OF ENKEPHALIN CATABOLISM INHIBITORS AND CCK-B ANTAGONISTS- A POTENTIAL USE IN THE MANAGEMENT OF PAIN AND OPIOID ADDICTION

The overlapping distribution of opioid and cholecystokinin (CCK) pepti des and their receptors (mu and delta opioid receptors; CCK-A and CCK- B receptors) in the central nervous system have led to a large number of studies aimed at clarifying the functional relationships between th ese two neuropeptides. Most of the pharmacological studies devoted to the role of CCK and enkephalins have been focused on the control of pa in. Recently the existence of regulatory mechanisms between both syste ms have been proposed, and the physiological antagonism between CCK an d endogenous opioid systems has been definitely demonstrated by coadmi nistration of CCK-B selective antagonists with RB 101, a systemically active inhibitor, which fully protects enkephalins from their degradat ion. Several studies have also been done to investigate the functional relationships between both systems in development of opioid side-effe cts and in behavioral responses. This article will review the experime ntal pharmacology of association of enkephalin-degrading enzyme inhibi tors and CCK-B antagonists to demonstrate the interest of these molecu les in the management of both pain and opioid addiction.