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GSK-189,254: Wikis


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Systematic (IUPAC) name
ATC code  ?
PubChem 9798547
Chemical data
Formula C21H25N3O2 
Mol. mass 351.441 g/mol
SMILES eMolecules & PubChem
Therapeutic considerations
Pregnancy cat.  ?
Legal status

GSK-189,254 is a potent and selective H3-receptor inverse agonist developed by GlaxoSmithKline. It has subnanomolar affinity for the H3 receptor (Ki 0.2nM) and selectivity of over 10,000x for H3 over other histamine receptor subtypes.[1] Animal studies have shown it to possess not only stimulant and nootropic effects,[2] but also analgesic action suggesting a role for H3 receptors in pain processing in the spinal cord.[3] GSK-189,254 and several other related drugs are currently being investigated as a treatment for Alzheimer's disease and other forms of dementia,[4] as well as possible use in the treatment of conditions such as neuropathic pain which do not respond well to conventional analgesic drugs.[5]


  1. ^ Medhurst AD, Atkins AR, Beresford IJ, Brackenborough K, Briggs MA, Calver AR, Cilia J, Cluderay JE, Crook B, Davis JB, Davis RK, Davis RP, Dawson LA, Foley AG, Gartlon J, Gonzalez MI, Heslop T, Hirst WD, Jennings C, Jones DN, Lacroix LP, Martyn A, Ociepka S, Ray A, Regan CM, Roberts JC, Schogger J, Southam E, Stean TO, Trail BK, Upton N, Wadsworth G, Wald JA, White T, Witherington J, Woolley ML, Worby A, Wilson DM. GSK189254, a novel H3 receptor antagonist that binds to histamine H3 receptors in Alzheimer's disease brain and improves cognitive performance in preclinical models. Journal of Pharmacology and Experimental Therapeutics. 2007 Jun;321(3):1032-45. PMID 17327487
  2. ^ Le S, Gruner JA, Mathiasen JR, Marino MJ, Schaffhauser H. Correlation between ex vivo receptor occupancy and wake-promoting activity of selective H3 receptor antagonists. Journal of Pharmacology and Experimental Therapeutics. 2008 Jun;325(3):902-9. PMID 18305012
  3. ^ Medhurst SJ, Collins SD, Billinton A, Bingham S, Dalziel RG, Brass A, Roberts JC, Medhurst AD, Chessell IP. Novel histamine H3 receptor antagonists GSK189254 and GSK334429 are efficacious in surgically-induced and virally-induced rat models of neuropathic pain. Pain. 2008 Aug 15;138(1):61-9. PMID 18164820
  4. ^ Esbenshade TA, Browman KE, Bitner RS, Strakhova M, Cowart MD, Brioni JD. The histamine H3 receptor: an attractive target for the treatment of cognitive disorders. British Journal of Pharmacology. 2008 Jul;154(6):1166-81. PMID 18469850
  5. ^ Medhurst AD, Briggs MA, Bruton G, Calver AR, Chessell I, Crook B, Davis JB, Davis RP, Foley AG, Heslop T, Hirst WD, Medhurst SJ, Ociepka S, Ray A, Regan CM, Sargent B, Schogger J, Stean TO, Trail BK, Upton N, White T, Orlek B, Wilson DM. Structurally novel histamine H3 receptor antagonists GSK207040 and GSK334429 improve scopolamine-induced memory impairment and capsaicin-induced secondary allodynia in rats. Biochemical Pharmacology. 2007 Apr 15;73(8):1182-94. PMID 17276409


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