GSK-189,254

Identifiers

IUPAC name

* 6-[(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)oxy]-N-methylpyridine-3-carboxamide

CAS Number|

* 720690-73-3 N

PubChem CID|

* 9798547

ChemSpider|

* 7974313 N

UNII|

* 5T4TX6CO53

ChEMBL|

* ChEMBL517140 N

Chemical and physical data
Formula| C21H25N3O2
Molar mass| 351.441 g/mol g·mol−1
3D model (JSmol)|

* Interactive image

SMILES

* c4cc1CCN(C3CCC3)CCc1cc4Oc(cc2)ncc2C(=O)NC

InChI

* 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) N

* Key:WROHEWWOCPRMIA-UHFFFAOYSA-N N

NY (what is this?) (verify)

GSK-189,254 is a potent and selective H3 histamine 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 narcolepsy,[5] or neuropathic pain which do not respond well to conventional analgesic drugs.[6]

## References

1. ↑ "GSK189254, a novel H3 receptor antagonist that binds to histamine H3 receptors in Alzheimer's disease brain and improves cognitive performance in preclinical models". The Journal of Pharmacology and Experimental Therapeutics 321 (3): 1032–45. June 2007. doi:10.1124/jpet.107.120311. PMID 17327487.
2. ↑ "Correlation between ex vivo receptor occupancy and wake-promoting activity of selective H3 receptor antagonists". The Journal of Pharmacology and Experimental Therapeutics 325 (3): 902–9. June 2008. doi:10.1124/jpet.107.135343. PMID 18305012.
3. ↑ "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. August 2008. doi:10.1016/j.pain.2007.11.006. PMID 18164820.
4. ↑ "The histamine H3 receptor: an attractive target for the treatment of cognitive disorders". British Journal of Pharmacology 154 (6): 1166–81. July 2008. doi:10.1038/bjp.2008.147. PMID 18469850.
5. ↑ "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. May 2009. doi:10.1111/j.1476-5381.2009.00205.x. PMID 19413575.
6. ↑ "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. April 2007. doi:10.1016/j.bcp.2007.01.007. PMID 17276409.

* v
* t
* e

Histamine receptor modulators

H1|

* Agonists: 2-Pyridylethylamine
* Betahistine
* Histamine
* HTMT
* L-Histidine
* UR-AK49

* Antagonists: First-generation: 4-Methyldiphenhydramine
* Alimemazine
* Antazoline
* Azatadine
* Bamipine
* Benzatropine (benztropine)
* Bepotastine
* Bromazine
* Brompheniramine
* Buclizine
* Captodiame
* Carbinoxamine
* Chlorcyclizine
* Chloropyramine
* Chlorothen
* Chlorphenamine
* Chlorphenoxamine
* Cinnarizine
* Clemastine
* Clobenzepam
* Clocinizine
* Cloperastine
* Cyclizine
* Cyproheptadine
* Dacemazine
* Decloxizine
* Deptropine
* Dexbrompheniramine
* Dexchlorpheniramine
* Dimenhydrinate
* Dimetindene
* Diphenhydramine
* Diphenylpyraline
* Doxylamine
* Embramine
* Etodroxizine
* Etybenzatropine (ethylbenztropine)
* Etymemazine
* Fenethazine
* Flunarizine
* Histapyrrodine
* Homochlorcyclizine
* Hydroxyethylpromethazine
* Hydroxyzine
* Isopromethazine
* Isothipendyl
* Meclozine
* Medrylamine
* Mepyramine (pyrilamine)
* Mequitazine
* Methafurylene
* Methapyrilene
* Methdilazine
* Moxastine
* Orphenadrine
* Oxatomide
* Oxomemazine
* Perlapine
* Phenindamine
* Pheniramine
* Phenyltoloxamine
* Pimethixene
* Piperoxan
* Pipoxizine
* Promethazine
* Propiomazine
* Pyrrobutamine
* Talastine
* Thenalidine
* Thenyldiamine
* Thiazinamium
* Thonzylamine
* Tolpropamine
* Tripelennamine
* Triprolidine

* Second/third-generation: Acrivastine
* Alinastine
* Astemizole
* Azelastine
* Bamirastine
* Barmastine
* Bepiastine
* Bepotastine
* Bilastine
* Cabastinen
* Carebastine
* Cetirizine
* Clemastine
* Clemizole
* Clobenztropine
* Desloratadine
* Dorastine
* Ebastine
* Efletirizine
* Emedastine
* Epinastine
* Fexofenadine
* Flezelastine
* Ketotifen
* Latrepirdine
* Levocabastine
* Levocetirizine
* Linetastine
* Loratadine
* Mapinastine
* Mebhydrolin
* Mizolastine
* Moxastine
* Noberastine
* Octastine
* Olopatadine
* Perastine
* Pibaxizine
* Piclopastine
* Quifenadine (phencarol)
* Rocastine
* Rupatadine
* Setastine
* Sequifenadine (bicarphen)
* Talastine
* Temelastine
* Terfenadine
* Vapitadine
* Zepastine

* Others: Atypical antipsychotics (e.g., aripiprazole, asenapine, Chemistry:Brexpiprazole

H2|

* Agonists: Amthamine
* Betazole
* Dimaprit
* Histamine
* HTMT
* Impromidine
* L-Histidine
* UR-AK49

* Antagonists: Bisfentidine
* Burimamide
* Cimetidine
* Dalcotidine
* Donetidine
* Ebrotidine
* Etintidine
* Famotidine
* Isolamtidine
* Lafutidine
* Lamtidine
* Lavoltidine (loxtidine)
* Lupitidine
* Metiamide
* Mifentidine
* Niperotidine
* Nizatidine
* Osutidine
* Oxmetidine
* Pibutidine
* Quisultazine (quisultidine)
* Ramixotidine
* Ranitidine
* Roxatidine
* Sufotidine
* Tiotidine
* Tuvatidine
* Venritidine
* Xaltidine
* Zolantidine

H3|

* Agonists: α-Methylhistamine
* Cipralisant
* Histamine
* Imetit
* Immepip
* Immethridine
* L-Histidine
* Methimepip
* Proxyfan

* Antagonists: A-349,821
* A-423,579
* ABT-239
* ABT-652
* AZD5213
* Bavisant
* Betahistine
* Burimamide
* Ciproxifan
* Clobenpropit
* Conessine
* Enerisant
* GSK-189,254
* Impentamine
* Iodophenpropit
* Irdabisant
* JNJ-5207852
* NNC 38-1049
* PF-03654746
* Pitolisant
* SCH-79687
* Thioperamide
* VUF-5681

H4|

* Agonists: 4-Methylhistamine
* α-Methylhistamine
* Histamine
* L-Histidine
* OUP-16
* VUF-8430

* Antagonists: JNJ-7777120
* Mianserin
* Seliforant
* Thioperamide
* Toreforant
* VUF-6002

See also: Receptor/signaling modulators • Monoamine metabolism modulators • Monoamine reuptake inhibitors

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