CONCEPTS FOR THE DESIGN OF 5-HT(1A) SEROTONIN AGONISTS AND ANTAGONISTS

The accessibility and use of a standard 5-HT1A agonist radioligand ([H-3]8-hydroxy-2-(dipropylamino)tetralin) has resulted in the availability of a large amount of binding data on various serotonergic agents. This, in turn, has permitted the formulation of structure-affinity relationships (SAFIR). By contrast, much less information is available concerning the agonist and antagonist activity of these agents. This is primarily due to a lack of standard evaluation procedures, controversy regarding the presynaptic versus postsynaptic nature of certain models, and the recent realization that many 5-HT1A agents are partial agonists. Thus, it has been difficult to formulate structure-activity relationships (SAR) for these agents. The present review examines the various classes of 5-HT1A serotonergic agents and the available data on their 5-HT1A agonist and antagonist activity with the aim of formulating SAR. These SAR should provide useful information for the subsequent design of 5-HT1A-selective agonists and antagonists.