GSK-189,254 is a potent and selective
H3 histamine receptorinverse 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
^Medhurst AD, Atkins AR, Beresford IJ, Brackenborough K, Briggs MA, Calver AR, et al. (June 2007). "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.
doi:
10.1124/jpet.107.120311.
PMID17327487.
S2CID14312511.
^Le S, Gruner JA, Mathiasen JR, Marino MJ, Schaffhauser H (June 2008). "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.
doi:
10.1124/jpet.107.135343.
PMID18305012.
S2CID26536000.
^Medhurst SJ, Collins SD, Billinton A, Bingham S, Dalziel RG, Brass A, et al. (August 2008). "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.
doi:
10.1016/j.pain.2007.11.006.
PMID18164820.
S2CID43724064.