GSK-189254

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 500804

CAS#: 945493-87-8

Description: GSK-189254 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.Animal studies have shown it to possess not only stimulant and nootropic effects, but also analgesic action suggesting a role for H3 receptors in pain processing in the spinal cord. GSK-189,254 and several other related drugs are currently being investigated as a treatment for Alzheimer's disease and other forms of dementia, as well as possible use in the treatment of conditions such as narcolepsy, or neuropathic pain which do not respond well to conventional analgesic drugs. (source: http://en.wikipedia.org/wiki/GSK-189,254).


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GSK-189254, purity > 98%, is in stock. The same day shipping out after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 500804
Name: GSK-189254
CAS#: 945493-87-8
Chemical Formula: C21H25N3O2
Exact Mass: 351.19468
Molecular Weight: 351.44
Elemental Analysis: C, 71.77; H, 7.17; N, 11.96; O, 9.10


Synonym: GSK189254; GSK-189254; GSK 189254.

IUPAC/Chemical Name: 6-((3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)oxy)-N-methylnicotinamide

InChi Key: WROHEWWOCPRMIA-UHFFFAOYSA-N

InChi Code: InChI=1S/C21H25N3O2/c1-22-21(25)17-6-8-20(23-14-17)26-19-7-5-15-9-11-24(18-3-2-4-18)12-10-16(15)13-19/h5-8,13-14,18H,2-4,9-12H2,1H3,(H,22,25)

SMILES Code: O=C(NC)C1=CN=C(OC2=CC=C3CCN(C4CCC4)CCC3=C2)C=C1


Technical Data

Appearance:
solid powder

Purity:
>98%

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>5 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

  
  
 
 


References

1: Regional Differential Effects of the Novel Histamine H3 Receptor Antagonist 6-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254) on Histamine Release in the Central Nervous System of Freely Moving Rats Patrizia Giannoni, Andrew D. Medhurst, Maria Beatrice Passani, Maria Grazia Giovannini, Chiara Ballini, Laura Della Corte, Patrizio Blandina J Pharmacol Exp Ther. 2010 January; 332(1): 164–172. doi: 10.1124/jpet.109.158444 PMCID: PMC2802467

2: Differential effects of acute and repeat dosing with the H3 antagonist GSK189254 on the sleep–wake cycle and narcoleptic episodes in Ox−/− mice RX Guo, C Anaclet, JC Roberts, R Parmentier, M Zhang, G Guidon, C Buda, JP Sastre, JQ Feng, P Franco, SH Brown, N Upton, AD Medhurst, JS Lin Br J Pharmacol. 2009 May; 157(1): 104–117. doi: 10.1111/j.1476-5381.2009.00205.x PMCID: PMC2697793

3: Characterization of histamine H3 receptors in Alzheimer's Disease brain and amyloid over-expressing TASTPM mice AD Medhurst, JC Roberts, J Lee, CPL-H Chen, SH Brown, S Roman, MKP Lai Br J Pharmacol. 2009 May; 157(1): 130–138. doi: 10.1111/j.1476-5381.2008.00075.x PMCID: PMC2697792

4: The histamine H3 receptor: an attractive target for the treatment of cognitive disorders T A Esbenshade, K E Browman, R S Bitner, M Strakhova, M D Cowart, J D Brioni Br J Pharmacol. 2008 July; 154(6): 1166–1181. Published online 2008 May 12. doi: 10.1038/bjp.2008.147 PMCID: PMC2483387

5: H3 Receptors and Pain Modulation: Peripheral, Spinal, and Brain Interactions Lindsay B. Hough, Frank L. Rice J Pharmacol Exp Ther. 2011 January; 336(1): 30–37. doi: 10.1124/jpet.110.171264 PMCID: PMC3014298

6: Ciproxifan, an H3 Receptor Antagonist, Alleviates Hyperactivity and Cognitive Deficits in the APPTg2576 Mouse Model of Alzheimer’s Disease Mark E. Bardgett, Natasha N. Davis, Patrick J. Schultheis, Molly S. Griffith Neurobiol Learn Mem. Author manuscript; available in PMC 2012 January 1.Published in final edited form as: Neurobiol Learn Mem. 2011 January; 95(1): 64–72. Published online 2010 November 10. doi: 10.1016/j.nlm.2010.10.008 PMCID: PMC3034295

7: Histamine neurons in the tuberomamillary nucleus: a whole center or distinct subpopulations? Patrizio Blandina, Leonardo Munari, Gustavo Provensi, Maria B. Passani Front Syst Neurosci. 2012; 6: 33. Published online 2012 May 4. doi: 10.3389/fnsys.2012.00033 PMCID: PMC3343474

8: Histamine H3 Receptor: A Novel Therapeutic Target in Alcohol Dependence? Saara Nuutinen, Jenni Vanhanen, Tiia Mäki, Pertti Panula Front Syst Neurosci. 2012; 6: 36. Published online 2012 May 18. doi: 10.3389/fnsys.2012.00036 PMCID: PMC3355329

9: HISTAMINE IN THE REGULATION OF WAKEFULNESS Mahesh M. Thakkar Sleep Med Rev. Author manuscript; available in PMC 2012 February 1.Published in final edited form as: Sleep Med Rev. 2011 February; 15(1): 65–74. Published online 2010 September 20. doi: 10.1016/j.smrv.2010.06.004 PMCID: PMC3016451

10: Advances in histamine pharmacology reveal new drug targets Paul L Chazot Br J Pharmacol. 2009 May; 157(1): 1–3. doi: 10.1111/j.1476-5381.2009.00228.x PMCID: PMC2697794

11: Approaches to Measuring the Effects of Wake-Promoting Drugs: A Focus on Cognitive Function Christopher J. Edgar, Edward F. Pace-Schott, Keith A. Wesnes Hum Psychopharmacol. Author manuscript; available in PMC 2010 July 1.Published in final edited form as: Hum Psychopharmacol. 2009 July; 24(5): 371–389. doi: 10.1002/hup.1034 PMCID: PMC2747813

12: White and Gray Matter Abnormalities in Narcolepsy with Cataplexy Christoph Scherfler, Birgit Frauscher, Michael Schocke, Michael Nocker, Viola Gschliesser, Laura Ehrmann, Markus Niederreiter, Regina Esterhammer, Klaus Seppi, Elisabeth Brandauer, Werner Poewe, Birgit Högl Sleep. 2012 March 1; 35(3): 345–351. doi: 10.5665/sleep.1692 PMCID: PMC3274335

13: Effects of methimepip and JNJ-5207852 in Wistar rats exposed to an open-field with and without object and in Balb/c mice exposed to a radial-arm maze Rushdie M. A. Abuhamdah, Ruan van Rensburg, Natasha L. Lethbridge, Abdel Ennaceur, Paul L. Chazot Front Syst Neurosci. 2012; 6: 54. Published online 2012 July 16. doi: 10.3389/fnsys.2012.00054 PMCID: PMC3397409

14: Newer molecules in the treatment of schizophrenia: A clinical update Abhishek Ghosh, Kaustav Chakraborty, Surendra Kumar Mattoo Indian J Pharmacol. 2011 April; 43(2): 105–112. doi: 10.4103/0253-7613.77334 PMCID: PMC3081445

15: Spinal Astrocytic Activation Is Involved in a Virally-Induced Rat Model of Neuropathic Pain Gui-He Zhang, Miao-Miao Lv, Shuang Wang, Lei Chen, Nian-Song Qian, Yu Tang, Xu-Dong Zhang, Peng-Cheng Ren, Chang-Jun Gao, Xu-De Sun, Li-Xian Xu PLoS One. 2011; 6(9): e23059. Published online 2011 September 28. doi: 10.1371/journal.pone.0023059 PMCID: PMC3182161

16: In vivo brain microdialysis: advances in neuropsychopharmacology and drug discovery Altaf S. Darvesh, Richard T. Carroll, Werner J. Geldenhuys, Gary A. Gudelsky, Jochen Klein, Charles K. Meshul, Cornelis J. Van der Schyf Expert Opin Drug Discov. Author manuscript; available in PMC 2012 February 1.Published in final edited form as: Expert Opin Drug Discov. 2011 February; 6(2): 109–127. doi: 10.1517/17460441.2011.547189 PMCID: PMC3083031

17: The histamine H3 receptor: from discovery to clinical trials with pitolisant Jean-Charles Schwartz Br J Pharmacol. 2011 June; 163(4): 713–721. doi: 10.1111/j.1476-5381.2011.01286.x PMCID: PMC3111674

18: Narcolepsy: a review Gbolagade Sunmaila Akintomide, Hugh Rickards Neuropsychiatr Dis Treat. 2011; 7: 507–518. Published online 2011 September 8. doi: 10.2147/NDT.S23624 PMCID: PMC3173034

19: Alzheimer’s Disease and Age-Related Memory Decline (Preclinical) Alvin V. Terry, Jr, Patrick M. Callahan, Brandon Hall, Scott J. Webster Pharmacol Biochem Behav. Author manuscript; available in PMC 2012 August 1.Published in final edited form as: Pharmacol Biochem Behav. 2011 August; 99(2): 190–210. Published online 2011 February 24. doi: 10.1016/j.pbb.2011.02.002 PMCID: PMC3113643

20: Rodent Models of Varicella-Zoster Virus Neurotropism Jeffrey I. Cohen Curr Top Microbiol Immunol. Author manuscript; available in PMC 2012 August 2.Published in final edited form as: Curr Top Microbiol Immunol. 2010; 342: 277–289. doi: 10.1007/82_2010_11 PMCID: PMC3410751

21: Histamine H3 receptor activation decreases kainate-induced hippocampal gamma oscillations in vitro by action potential desynchronization in pyramidal neurons Richard Andersson, Maria Lindskog, André Fisahn J Physiol. 2010 April 15; 588(Pt 8): 1241–1249. Published online 2010 February 15. doi: 10.1113/jphysiol.2009.180984 PMCID: PMC2872730

22: The multiple pathways for itch and their interactions with pain Steve Davidson, Glenn J Giesler Trends Neurosci. Author manuscript; available in PMC 2011 December 1.Published in final edited form as: Trends Neurosci. 2010 December; 33(12): 550–558. Published online 2010 November 5. doi: 10.1016/j.tins.2010.09.002 PMCID: PMC2991051

23: Pharmacological Enhancement of Memory and Executive Functioning in Laboratory Animals Stan B Floresco, James D Jentsch Neuropsychopharmacology. 2011 January; 36(1): 227–250. Published online 2010 September 15. doi: 10.1038/npp.2010.158 PMCID: PMC3055518

24: The H3 Antagonist, Ciproxifan, Alleviates the Memory Impairment but Enhances the Motor Effects of MK-801 (Dizocilpine) in Rats. Mark E. Bardgett, Megan Points, Jennifer Kleier, Meredith Blankenship, Molly S. Griffith Neuropharmacology. Author manuscript; available in PMC 2011 November 1.Published in final edited form as: Neuropharmacology. 2010 November; 59(6): 492–502. Published online 2010 July 16. doi: 10.1016/j.neuropharm.2010.07.004 PMCID: PMC2946466

25: Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia Jared W YOUNG, Susan POWELL, Victoria RISBROUGH, Hugh M MARSTON, Mark A GEYER Pharmacol Ther. Author manuscript; available in PMC 2009 June 1.Published in final edited form as: Pharmacol Ther. 2009 May; 122(2): 150–202. Published online 2009 March 6. doi: 10.1016/j.pharmthera.2009.02.004 PMCID: PMC2688712

26: Use of the H3 receptor antagonist radioligand [3H]-A-349821 to reveal in vivo receptor occupancy of cognition enhancing H3 receptor antagonists TR Miller, I Milicic, J Bauch, J Du, B Surber, KE Browman, K Marsh, M Cowart, JD Brioni, TA Esbenshade Br J Pharmacol. 2009 May; 157(1): 139–149. doi: 10.1111/j.1476-5381.2009.00239.x PMCID: PMC2697797