Serotonin receptors and site-selective agents

Few site-selective serotonergic agents are currently available; in fact, most of these agents might more appropriately be termed semi-selective in that they typically bind to at least two different populations of serotonin receptors. We describe the application of structure-affinity relationship (SAFIR) studies to the development of high- affinity and/or site-selective serotonergic agents; examples are provided from work conducted in our laboratories. Also discussed is the concept of selectively non-selective agents and their potential preclinical and clinical utility. A case is made for development of selective and nonselective serotonergic agents.