A Novel Opioid Receptor Site Directed Alkylating Agent with Irreversible Narcotic Antagonistic and Reversible Agonistic Activities

Sir: In 1965 the concept of multiple opioid receptors and multiple modes of interaction with a single receptor was proposed based on a detailed analysis of a broad spectrum of structure-activity relationships among analgetic ligands. The major lines of evidence for this concept were (1) the divergent stereochemical requirements for analgetic activity and (2) the different rank-order potencies among congeners, in two or more series, whose N substituent is modified in an identical manner.