|Chemical and physical data|
|Molar mass||451.98 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
SB-271046 is a drug which is used in scientific research. It was one of the first selective 5-HT6 receptor antagonists to be discovered, and was found through high-throughput screening of the SmithKline Beecham Compound Bank using cloned 5-HT6 receptors as a target, with an initial lead compound being developed into SB-271046 through a structure-activity relationship (SAR) study. SB-271046 was found to be potent and selective in vitro and had good oral bioavailability in vivo, but had poor penetration across the blood–brain barrier, so further SAR work was then conducted, which led to improved 5-HT6 antagonists such as SB-357,134 and SB-399,885.
SB-271046 was found to increase levels of the excitatory amino acid neurotransmitters glutamate and aspartate, as well as dopamine and noradrenaline in the frontal cortex and hippocampus of rats, and 5-HT6 antagonists have been shown to produce nootropic effects in a variety of animal studies. Suggested applications of these drugs include treatment of schizophrenia and other psychiatric disorders.
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- Dawson LA, Nguyen HQ, Li P (November 2001). "The 5-HT(6) receptor antagonist SB-271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus". Neuropsychopharmacology. 25 (5): 662–8. doi:10.1016/S0893-133X(01)00265-2. PMID 11682249.
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- Foley AG, Murphy KJ, Hirst WD, Gallagher HC, Hagan JJ, Upton N, et al. (January 2004). "The 5-HT(6) receptor antagonist SB-271046 reverses scopolamine-disrupted consolidation of a passive avoidance task and ameliorates spatial task deficits in aged rats". Neuropsychopharmacology. 29 (1): 93–100. doi:10.1038/sj.npp.1300332. PMID 14571256.
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- de Foubert G, O'Neill MJ, Zetterström TS (July 2007). "Acute onset by 5-HT(6)-receptor activation on rat brain brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein mRNA expression". Neuroscience. 147 (3): 778–85. doi:10.1016/j.neuroscience.2007.04.045. PMID 17560041.
- Marcos B, Aisa B, Ramírez MJ (March 2008). "Functional interaction between 5-HT(6) receptors and hypothalamic-pituitary-adrenal axis: cognitive implications". Neuropharmacology. 54 (4): 708–14. doi:10.1016/j.neuropharm.2007.11.019. PMID 18206183.
- Loiseau F, Dekeyne A, Millan MJ (January 2008). "Pro-cognitive effects of 5-HT6 receptor antagonists in the social recognition procedure in rats: implication of the frontal cortex". Psychopharmacology. 196 (1): 93–104. doi:10.1007/s00213-007-0934-5. PMID 17922111.
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