Silent 5-HT<inf>1A</inf>receptor antagonists: utility as research tools and therapeutic agents

The 5-hydroxytryptamine 5-HT1Areceptor has been the focus of considerable research effort for over a decade. However, the definitive classification of this receptor and the full characterization of its pharmacology have awaited the development of highly selective 5-HT1Areceptor antagonists. The only compounds available until recently have been either nonselective or partial 5-HT1Areceptor agonists (or a combination of both). Confusion has arisen owing to the use of different pharmacological models in examining the functional activity of 5-HT1Areceptor ligands. Several partial agonists display only antagonist activity in models of postsynaptic 5-HT1Areceptor function, whereas their agonist properties are revealed in models of presynaptic, somatodendritic 5-HT1Aautoreceptor function. In view of these considerations, the term 'silent antagonist' has been introduced to distinguish true 5-HT1Areceptor antagonists from partial agonists. Allan Fletcher and colleagues review the pharmacological properties of the first selective silent 5-HT1Areceptor antagonists that have been recently discovered and discuss the potential therapeutic utility of these novel compounds. © 1993.