GSK-189,254

GSK-189,254
IUPAC ime
	6-[(3-Ciklobutil-2,3,4,5-tetrahidro-1H-3-benzazepin-7-il)oksi]-N-metil-3-piridinekarboksamid
Identifikatori
ATC kod	none
PubChem	CID 9798547
ChEMBL	CHEMBL517140
Hemijski podaci
Formula	C21H25N3O2
Molarna masa	351,441 g/mol
	SMILES c4cc1CCN(C3CCC3)CCc1cc4Oc(cc2)ncc2C(=O)NC; ;

GSK-189,254 je potentan i selektivan inverzni agonist H₃-receptor koji jer razvila kompanija GlaxoSmithKline. On ima subnanomolarni afinitet za H₃ receptor (Ki 0.2 nM) i selektivnost preko 10.000 puta za H₃ u odnosu na druge tipove histaminskog receptora.^[1] Životinjske studije su pokazale da poseduje ne samo stimulansne i nootropne efekte,^[2] nego i analgetičke iz čega sledi da H₃ receptori učestvuju u procesovanju signala bola u kičmenoj moždini.^[3]

GSK-189,254 i nekoliko drugih srodnih lekova se istražuju za moguću primenu u tretmanu Alchajmerove bolesti i drugih formi demencije,^[4] kao i za lečenje narkolepsije,^[5] ili neuropatskog bola na koji konvencionalni analgetici imaju malo uticaja.^[6]

Reference

^ 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. 321 (3): 1032—45. јун 2007. PMID 17327487. Недостаје или је празан параметар |title= (помоћ)
^ 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. 325 (3): 902—9. јун 2008. PMID 18305012. doi:10.1124/jpet.107.135343. .
^ 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. 138 (1): 61—9. август 2008. PMID 18164820. doi:10.1016/j.pain.2007.11.006. .
^ 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. 154 (6): 1166—81. јул 2008. PMID 18469850. doi:10.1038/bjp.2008.147. .
^ Guo RX, Anaclet C, Roberts JC, Parmentier R, Zhang M, Guidon G, Buda C, Sastre JP, Feng JQ, Franco P, Brown SH, Upton N, Medhurst AD, Lin JS. Differential effects of acute and repeat dosing with the H3 antagonist GSK189254 on the sleep-wake cycle and narcoleptic episodes in Ox-/- mice. British Journal of Pharmacology. 157 (1): 104—17. мај 2009. PMID 19413575. Недостаје или је празан параметар |title= (помоћ)
^ Medhurst, A. D.; Briggs MA; Bruton, G.; Calver, A. R.; 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 (април 2007). „Structurally novel histamine H3 receptor antagonists GSK207040 and GSK334429 improve scopolamine-induced memory impairment and capsaicin-induced secondary allodynia in rats”. Biochemical Pharmacology. 73 (8): 1182—94. PMID 17276409.

Spoljašnje veze

[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. 321 (3): 1032—45. јун 2007. PMID 17327487. Недостаје или је празан параметар |title= (помоћ)

[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. 325 (3): 902—9. јун 2008. PMID 18305012. doi:10.1124/jpet.107.135343. .

[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. 138 (1): 61—9. август 2008. PMID 18164820. doi:10.1016/j.pain.2007.11.006. .

[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. 154 (6): 1166—81. јул 2008. PMID 18469850. doi:10.1038/bjp.2008.147. .

[5] Guo RX, Anaclet C, Roberts JC, Parmentier R, Zhang M, Guidon G, Buda C, Sastre JP, Feng JQ, Franco P, Brown SH, Upton N, Medhurst AD, Lin JS. Differential effects of acute and repeat dosing with the H3 antagonist GSK189254 on the sleep-wake cycle and narcoleptic episodes in Ox-/- mice. British Journal of Pharmacology. 157 (1): 104—17. мај 2009. PMID 19413575. Недостаје или је празан параметар |title= (помоћ)

[6] Medhurst, A. D.; Briggs MA; Bruton, G.; Calver, A. R.; 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 (април 2007). „Structurally novel histamine H3 receptor antagonists GSK207040 and GSK334429 improve scopolamine-induced memory impairment and capsaicin-induced secondary allodynia in rats”. Biochemical Pharmacology. 73 (8): 1182—94. PMID 17276409.

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