Abstract
Publisher Summary The 5-HT6 receptor is one of the most recently discovered of the serotonin superfamily of receptors and is a part of the seven-transmembrane G-protein-coupled receptor family that positively couples to Gαs subunits and as such stimulates adenylate cyclase and increases cyclic adenosine monophosphate (cAMP) signaling cascades. This chapter describes the use of ligands through preclinical sampling techniques, such as in vivo microdialysis, discusses the modulatory role of the 5-HT 6 receptor on multiple neurotransmitter systems and networks within mammalian brain, and presents the underlying neurobiology of the observed changes along with the potential therapeutic implications and utility of both agonist and antagonist ligands in a range of neurobiological disorders. 5-HT 6 receptor ligands can subsequently produce a diverse series of changes in monoaminergic, cholinergic, and excitatory amino acid neurotransmission. The neurochemical data provide supportive evidence and suggest a number of therapeutic avenues that may be pursued for antagonist and, more recently, agonist ligands. This receptor offers much potential as a therapeutic intervention point for a range of central nervous system (CNS)-related disorders and the outcomes of current and future clinical evaluations are awaited with interest and hope.
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