Silent 5-HT1A receptor antagonists: utility as research tools and therapeutic agents.
The 5-hydroxytryptamine 5-HT1A receptor 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-HT1A receptor antagonists. The only compounds available until recently have been either nonselective or partial 5-HT1A receptor agonists (or a combination of both). Confusion has arisen owing to the use of different pharmacological models in examining the functional activity of 5-HT1A receptor ligands. Several partial agonists display only antagonist activity in models of postsynaptic 5-HT1A receptor function, whereas their agonist properties are revealed in models of presynaptic, somatodendritic 5-HT1A autoreceptor function. In view of these considerations, the term 'silent antagonist' has been introduced to distinguish true 5-HT1A receptor antagonists from partial agonists. Allan Fletcher and colleagues review the pharmacological properties of the first selective silent 5-HT1A receptor antagonists that have been recently discovered and discuss the potential therapeutic utility of these novel compounds.
Fletcher
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Wyeth Research, Berkshire, UK.
Cliffe
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Dourish
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CT
D000818:Animals; D001665:Binding Sites; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy*; D051381:Rats; D011985:Receptors, Serotonin / Q000145:classification / Q000378:metabolism; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists