| Identification | Back Directory | [Name]
GSK 189254A | [CAS]
720690-73-3 | [Synonyms]
GSK 189254A
6-(3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy)-N-MethylnicotinaMide
N-(4-METHOXYBENZYL)-1-[(4-METHYLPHENYL)SULFONYL]-1H-PYRROLO[2,3-B]PYRIDIN-4-AMINE | [Molecular Formula]
C21H25N3O2 | [MOL File]
720690-73-3.mol | [Molecular Weight]
351.44 |
| Chemical Properties | Back Directory | [Boiling point ]
545.0±50.0 °C(Predicted) | [density ]
1.195±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:25.0(Max Conc. mg/mL);71.13(Max Conc. mM) | [form ]
A solid | [pka]
14.26±0.46(Predicted) | [color ]
White to off-white |
| Questions And Answer | Back Directory | [Description]
GSK189254A is a histamine H3 receptor antagonist for the treatment of narcolepsy.It may also be useful for the treatment of dementia and neuropathic pain. Its pharmacological effect may be related to its effect on increasing the release neurotransmitter in the brain. Microdialysis studies demonstrated that GSK189254 increased the release of acetylcholine, noradrenaline, and dopamine in the anterior cingulate cortex and acetylcholine in the dorsal hippocampus. GSK189254 significantly improved performance of rats in diverse cognition paradigms, including passive avoidance, water maze, object recognition, and attentional set shift. These data suggest that GSK189254 may have therapeutic potential for the symptomatic treatment of dementia in Alzheimer's disease and other cognitive disorders.
| [References]
Medhurst, Andrew D., and A. I. J. Beresford. "GSK189254, a novel H3 receptor antagonist that binds to histamine H3 receptors in Alzheimer's disease brain and improves cognitive performance in preclinical models." Alzheimers & Dementia 321.3(2007):1032.
Plisson, Christophe, et al. "PET imaging of the CNS histamine H3 receptor using [11C] GSK189254A." Neuroimage 31.1(2006):T47-T47.
http://medkoo.com/products/10117
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| Hazard Information | Back Directory | [Uses]
GSK189254A (GSK189254 free base) is a novel, potent and selective histamine H3 receptor antagonist with pKi values of 9.59-9.90 and 8.51-9.17 for human and rat H3, respectively. | [in vivo]
GSK189254 (0.3-3 mg/kg p.o.) increases the release of acetylcholine, noradrenaline, and dopamine in the anterior cingulate cortex and acetylcholine in the dorsal hippocampus. GSK189254 significantly improves performance of rats in diverse cognition paradigms, including passive avoidance, water maze, object recognition, and attentional set shift[1]. In Ox+/+ and Ox?/? mice, acute administration of GSK189254 increases W and decreases slow wave and paradoxical sleep to a similar degree to modafinil, while it reduces narcoleptic episodes in Ox?/? mice[2]. | [IC 50]
H3 receptor |
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