5-HT6 receptor

Overview

The 5-HT6 receptor is a GPCR that couples via Gs to increase cAMP production although additional transduction pathways have been proposed. The receptor is structurally differentiated from the other 5-HT... [read more] receptors with less than 34% amino acid sequence identity. Various selective 5-HT6 receptor antagonists have been described (e.g. SB742457) and selective agonists are becoming available (e.g. EMD386088).PharmacologyEMDT, EMD386088, and WAY181,187 are relatively selective 5-HT6 receptor agonists, and a number of selective antagonists have also been developed including SB399885, SB258585 and Ro4368554.Clinical significanceA number of non-selective drugs used to treat schizophrenia (e.g. asenapine, chlorpromazine, olanzepine, clozapine, zotepine), also display high affinity for the 5-HT6 receptor, although the consequences of this are not clear. These receptors are selectively expressed in the CNS, but mouse brain has a notably different regional pattern of expression in comparison to humans or rats. Relatively selective 5-HT6 antagonists induce precognitive effects in animal models, but little data has been generated in clinical populations. [close]