SB-271046 (SmithKline Beecham).
SmithKline Beecham is developing the 5-HT6 antagonist, SB-271046, as a potential cognition enhancer. By December 1999, phase I trials had commenced [360354]. This drug was originally being developed primarily for the treatment of shizophrenia [284490], however, cognitive disorders, including but not limited to Alzheimer's disease, have been the main target since 1998 [394309]. SB-271046 is a potent, selective 5-HT6 antagonist with a pKi value of 8.9 [333710]. SB-258585, also known as 4-iodo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide is an analog of SB-271046 [322488]. Data recently presented at the Society for Neuroscience annual meeting in November 2000 demonstrated that administration of SB-271046 resulted in a signficant increase in glutamate and aspartate levels in the frontal cortex, without affecting noradrenaline, dopamine or 5-HT levels. This was stated to suggest that 5-HT6 antagonists might therefore be useful for treating cognitive dysfunction [390469]. The drug has also been radiolabeled in order to provide an assay for estimating in vivo 5-HT6 receptor occupancy [390470].
Miguel-Hidalgo
J J
JJ
Department of Psychiatry and Human Behavior, University  of Mississippi Medical Center, Jackson 39216-4505, USA. jmiguel-hildago@psychiatry.umsmed.edu
D000818:Animals; D006801:Humans; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D013876:Thiophenes; C097216:serotonin 6 receptor; C117443:SB 271046