A Concise Review of Concepts in Opioid Pharmacology up to the Discovery of Endogenous Opioids.

Abstract

This brief review covers concepts in opioid pharmacology that were promoted during the period leading up to the establishment of the International Narcotics Research Conference (INRC) in the early 1970s and the discovery of endogenous opioid peptides in 1975. The founders of INRC, meeting together during the International Union of Pharmacology meeting in Basel in 1969, recognized that the time was ripe for the creation of an international society that would provide a venue for the discussion of research across disciplines in this rapidly expanding area of science. The emphasis here is on studies leading to the demonstration that specific receptors for morphine-like analgesics exist, the search for endogenous ligands for these receptors, and early attempts to elucidate the mechanisms underlying opiate drug tolerance, dependence, and addiction. SIGNIFICANCE STATEMENT: Research on opioids in the 20th century was driven by the search for nonaddicting analgesics. This review discusses the development of the "analgesic" receptor concept, the demonstration that such receptors existed, and the search for an endogenous ligand. Conceptual models were proposed to explain tolerance to the actions of opiate drugs and the development of dependence and addiction. This review explains these models and indicates how they foreshadowed more recent discoveries on the acute and chronic actions of opiate drugs.