Affinity Labels for Opioid Receptors

The concept of multiple opioid receptors and multiple modes of interaction with a single receptor emanated from two convergent lines of research. This proposal was based originally on a detailed analysis of a wide spectrum of structure-activity relationships among analgesic ligands (1, 2). Very soon, pharmacological studies complemented and provided a more detailed framework for this concept (3-5). More recently, the multiple receptor concept has been advanced through a number of in vitro and in vivo biological assays and the opioid receptor binding assay. Data from such studies have been summarized in a number of reviews (6-13). Based on a wide range of pharmacological tests in the chronic spinal dog, Martin and coworkers (14, 15) suggested the designation 1-'-, K, or IT for those receptors at which morphine, ketazocine, and SKF 10,047 (N-allyl­ normetazocine) respectively are postulated to interact. The notion of different receptors for morphine-like and ketazocineor nalorphine-like compounds has been strengthened by the use of the pA2 concept (16) both in vitro (17-19) and in vivo (5) and by various other testing methods in vivo (20-22). The 8 and E receptor through which the enkephalins and l3-endorphin respectively are thought to mediate their effects have been identified in vitro (19,23,24). Thea receptor in vivo has been implicated in a number of physiological functions