SB-271046: Difference between revisions

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| C=20 | H=22 | Cl=1 | N=3 | O=3 | S=2

| molecular_weight = 451.989 g/mol

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'''SB-271,046''' is a drug which is used in scientific research. It was one of the first selective [[5-HT6 receptor|5-HT₆]] [[Receptor (biochemistry)|receptor]] [[Antagonist (pharmacology)|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-271,046 through a [[structure-activity relationship]] (SAR) study.<ref>{{cite journal | last1 = Bromidge | first1 = SM | last2 = Brown | first2 = AM | last3 = Clarke | first3 = SE | last4 = Dodgson | first4 = K | last5 = Gager | first5 = T | last6 = Grassam | first6 = HL | last7 = Jeffrey | first7 = PM | last8 = Joiner | first8 = GF | last9 = King | first9 = FD | title = 5-Chloro-N-(4-methoxy-3-piperazin-1-yl- phenyl)-3-methyl-2-benzothiophenesulfon- amide (SB-271046): a potent, selective, and orally bioavailable 5-HT6 receptor antagonist | journal = Journal of medicinal chemistry | volume = 42 | issue = 2 | pages = 202–5 | year = 1999 | pmid = 9925723 | doi = 10.1021/jm980532e }}</ref> SB-271,046 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]].<ref>{{cite journal | last1 = Ahmed | first1 = M | last2 = Briggs | first2 = MA | last3 = Bromidge | first3 = SM | last4 = Buck | first4 = T | last5 = Campbell | first5 = L | last6 = Deeks | first6 = NJ | last7 = Garner | first7 = A | last8 = Gordon | first8 = L | last9 = Hamprecht | first9 = DW | title = Bicyclic heteroarylpiperazines as selective brain penetrant 5-HT6 receptor antagonists | journal = Bioorganic & medicinal chemistry letters | volume = 15 | issue = 21 | pages = 4867–71 | year = 2005 | pmid = 16143522 | doi = 10.1016/j.bmcl.2005.06.107 }}</ref>

SB-271,046 was found to increase levels of the excitatory [[amino acid]] [[neurotransmitter]]s [[glutamate]] and [[aspartate]],<ref>{{cite journal | last1 = Dawson | first1 = LA | last2 = Nguyen | first2 = HQ | last3 = Li | first3 = P | title = In vivo effects of the 5-HT(6) antagonist SB-271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5-HT, glutamate and aspartate | journal = British journal of pharmacology | volume = 130 | issue = 1 | pages = 23–6 | year = 2000 | pmid = 10780993 | pmc = 1572041 | doi = 10.1038/sj.bjp.0703288 }}</ref> as well as [[dopamine]] and [[noradrenaline]]<ref>{{cite journal | last1 = Lacroix | first1 = LP | last2 = Dawson | first2 = LA | last3 = Hagan | first3 = JJ | last4 = Heidbreder | first4 = CA | title = 5-HT6 receptor antagonist SB-271046 enhances extracellular levels of monoamines in the rat medial prefrontal cortex | journal = Synapse | volume = 51 | issue = 2 | pages = 158–64 | year = 2004 | pmid = 14618683 | doi = 10.1002/syn.10288 }}</ref> in the [[frontal cortex]] and [[hippocampus]] of rats,<ref>{{cite journal | last1 = Dawson | first1 = LA | last2 = Nguyen | first2 = HQ | last3 = Li | first3 = P | title = The 5-HT(6) receptor antagonist SB-271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus | journal = Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology | volume = 25 | issue = 5 | pages = 662–8 | year = 2001 | pmid = 11682249 | doi = 10.1016/S0893-133X(01)00265-2 }}</ref> and 5-HT₆ antagonists have been shown to produce [[nootropic]] effects in a variety of animal studies.<ref>{{cite journal | last1 = Rogers | first1 = DC | last2 = Hagan | first2 = JJ | title = 5-HT6 receptor antagonists enhance retention of a water maze task in the rat | journal = Psychopharmacology | volume = 158 | issue = 2 | pages = 114–9 | year = 2001 | pmid = 11702084 | doi = 10.1007/s002130100840 }}</ref><ref>{{cite journal | last1 = Foley | first1 = AG | last2 = Murphy | first2 = KJ | last3 = Hirst | first3 = WD | last4 = Gallagher | first4 = HC | last5 = Hagan | first5 = JJ | last6 = Upton | first6 = N | last7 = Walsh | first7 = FS | last8 = Regan | first8 = CM | title = 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 | journal = Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology | volume = 29 | issue = 1 | pages = 93–100 | year = 2004 | pmid = 14571256 | doi = 10.1038/sj.npp.1300332 }}</ref><ref>{{cite journal | last1 = Marcos | first1 = B | last2 = Chuang | first2 = TT | last3 = Gil-Bea | first3 = FJ | last4 = Ramirez | first4 = MJ | title = Effects of 5-HT6 receptor antagonism and cholinesterase inhibition in models of cognitive impairment in the rat | journal = British journal of pharmacology | volume = 155 | issue = 3 | pages = 434–40 | year = 2008 | pmid = 18622410 | pmc = 2567877 | doi = 10.1038/bjp.2008.281 }}</ref> Suggested applications of these drugs include treatment of [[schizophrenia]] and other psychiatric disorders.<ref>{{cite journal | last1 = Minabe | first1 = Y | last2 = Shirayama | first2 = Y | last3 = Hashimoto | first3 = K | last4 = Routledge | first4 = C | last5 = Hagan | first5 = JJ | last6 = Ashby Jr | first6 = CR | title = Effect of the acute and chronic administration of the selective 5-HT6 receptor antagonist SB-271046 on the activity of midbrain dopamine neurons in rats: an in vivo electrophysiological study | journal = Synapse | volume = 52 | issue = 1 | pages = 20–8 | year = 2004 | pmid = 14755629 | doi = 10.1002/syn.20002 }}</ref><ref>{{cite journal | last1 = De Foubert | first1 = G | last2 = O'Neill | first2 = MJ | last3 = Zetterström | first3 = TS | title = Acute onset by 5-HT(6)-receptor activation on rat brain brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein mRNA expression | journal = Neuroscience | volume = 147 | issue = 3 | pages = 778–85 | year = 2007 | pmid = 17560041 | doi = 10.1016/j.neuroscience.2007.04.045 }}</ref><ref>{{cite journal | last1 = Marcos | first1 = B | last2 = Aisa | first2 = B | last3 = Ramírez | first3 = MJ | title = Functional interaction between 5-HT(6) receptors and hypothalamic-pituitary-adrenal axis: cognitive implications | journal = Neuropharmacology | volume = 54 | issue = 4 | pages = 708–14 | year = 2008 | pmid = 18206183 | doi = 10.1016/j.neuropharm.2007.11.019 }}</ref><ref>{{cite journal | last1 = Loiseau | first1 = F | last2 = Dekeyne | first2 = A | last3 = Millan | first3 = MJ | title = Pro-cognitive effects of 5-HT6 receptor antagonists in the social recognition procedure in rats: implication of the frontal cortex | journal = Psychopharmacology | volume = 196 | issue = 1 | pages = 93–104 | year = 2008 | pmid = 17922111 | doi = 10.1007/s00213-007-0934-5 }}</ref>

==References==

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[[Category:Phenol ethers]]

[[Category:Organochlorides]]

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