U-50,488 and the kappa receptor: a personalized account covering the period 1973 to 1990.

All clinically significant analgesics for severe pain derive from the morphine model. Morphine has provided a fertile area for medicinal chemistry research and received an additional stimulus in the 1970s with the appearance of the opioid receptors. The background for the birth of U-50,488 is described herein. It occurred before the discovery of the kappa receptor and, thus, U-50,488 was classified originally as a non-mu compound, and only later as a kappa agonist. U-50,488 provided a succinct template for structural modifications and they are described for the period up to 1990. A description of the structural classes of kappa agonists is provided including a summary of kappa recognition sites based on known agonists.