A short history of the rise of the molecular pharmacology of ionotropic drug receptors

Remarkably, perhaps, for many pharmacologists today, just over 25 years ago, receptors were still considered hypothetical entities. The isolation and identification of Langley's receptive substance (Ehrlich's side-chains) required efforts from diverse groups; serendipity also facilitated its purification and subsequent biochemical and molecular characterization. In this review, I consider some of the key individuals and breakthrough technical developments from the late 1950s to the early 1990s that lead to the cloning of the first receptors. I focus on the nicotinic acetylcholine receptor to illustrate the complexities in this field and because it was the first receptor to be cloned. This brief history will also touch upon the implications of the rise of molecular pharmacology for the development of new drugs.