14. Opiate Receptors: Isolation and Mechanisms

Research on the mode of action of narcotic analgesic drugs and the mechanism of the development of tolerance and physical dependence is one of the oldest of scientific pursuits. For many years the first step in the action of these drugs was postulated to be their binding to highly specific "receptor" sites. This specific drug-receptor interaction was thought to trigger certain chemical or physical changes leading to the observed pharmacological responses. The reason for such a receptor postulate was the striking structural and steric specificity of many of the actions of narcotic Analgesics. Rather minor structural changes have major effects on the pharmacology of the molecule, leading in some instances to the formation of antagonists, drugs whose main action consists of counteracting the effects of other opiates. While the receptor postulate dates back two to three decades, the discovery of the existence of specific opiate receptors occurred only about three years ago.