Opioid Receptors and Endogenous Opioid Peptides

Abstract

According to Ariëns et al. (1964b), the concept of receptors was first proposed by J. N. Langley in 1905 to account for the actions of nicotine and curare at the myoneural junction, and by P. Ehrlich in 1906 to account for specific interactions between antigens and antibodies and for the selectivity of dyes for certain components of living cells. On the basis of his research, Ehrlich (1913) concluded that “If the law is true in chemistry that ‘corpora non agunt nisi liquida,’ then for chemotherapy the principle is true that ‘corpora non agunt nisi fixata”’ (substances do not act unless they are fixated). In modern drug-receptor interaction theory, reversible “fixation” of the drug to the receptor is held to produce the pharmacological effect, and drug-receptor interactions are viewed as analogous to substrate-enzyme interactions (Michaelis & Menten, 1913). In this view, subject to some qualifications expressed by Ariëns et al. (1956), the receptor concentration is regarded as if it were an enzyme concentration, the drug concentration as if it were a substrate concentration, and the pharmacological effect of the drug-receptor combination as if it were the initial reaction velocity of the enzyme-catalyzed substrate change. On the basis of these and some other assumptions, the dose-effect relationships of agonists, partial agonists, and antagonists, as well as their intrinsic activities (efficacies) and affinities, have been calculated. The term agonist implies that a given pharmacological effect of a drug increases with its dose (or its concentration) up to a maximum.