History and development of mixed opioid agonists, partial agonists and antagonists.

Abstract

1 A brief history of the development of narcotic antagonists is outlined. 2 The clinical and pharmacological observations leading to the discovery of dualism of opiate receptors are reviewed. 3 An extension of this theory to a three‐receptor model (mu, kappa and sigma) is required to rationalize the pharmacology of the antagonists analgesics cyclazocine, pentazocine and nalorphine. 4 The methodologies available for the study of compounds with dual agonist‐antagonist activity are discussed in the light of the above receptor multiplicity, and data appertaining to the kappa‐partial agonist, nalorphine and the mu‐partial agonist buprenorphine are outlined.