5564-19-2Relevant academic research and scientific papers
5-HT6 serotonin receptor binding of indolealkylamines: A preliminary structure-affinity investigation
Glennon, Richard A.,Bondarev, Mikhail,Roth, Bryan
, p. 108 - 117 (2007/10/03)
Serotonin receptors are classified as belonging to one of seven major families (5-HT1-5-HT7); one of the newest members is the 5-HT6 population of receptors. The possibility that this population of receptors may play a role in neuropsychiatric disorders has attracted considerable attention; but, to date, relatively little is known about the structural requirements for binding at 5-HT6 receptors. Beginning with 5-HT itself (5-HT6 Ki = 75 nM), we examined the contribution to binding of (a) the 5-position hydroxyl group, (b) aromatic methoxy substitution, (c) terminal amine substitution, (d) side chain lengthening, branching, and conformational restriction, and (d) the pyrrole ring. In addition to the formulation of structure-affinity relationships (SAFIR), a key findings of this investigation is that 2-methyl substitution of the indole nucleus is tolerated by 5-HT6 receptors (i.e., 2- methyl 5-HT6 Ki = 46 nM). This latter finding is significant because up until this time 2-methyl 5-HT has been considered a 5-HT3-selective agent (5-HT3 Ki ?1,000 nM).
