GSK189254A

Description: GSK189254A (also known as GSK189254) is a novel histamine H(3) receptor antagonist with high affinity for human (pK(i) = 9.59 -9.90) and rat (pK(i) = 8.51-9.17) H(3) receptors. It has the potential for the treatment of narcolepsy. GSK189254 is > 10, 000-fold selective for human H(3) receptors versus other targets tested, and it exhibited potent functional antagonism (pA(2) = 9.06 versus agonist-induced changes in cAMP) and inverse agonism pIC(50) = 8.20 versus basal guanosine 5'-O-(3-(35)Sthio)triphosphate binding at the human recombinant H(3) receptor. In vitro autoradiography demonstrated specific (3)HGSK189254 binding in rat and human brain areas, including cortex and hippocampus. GSK189254 may have therapeutic potential for the symptomatic treatment of dementia in Alzheimer's disease and other cognitive disorders.

References: J Pharmacol Exp Ther. 2007 Jun; 321(3):1032-45; Br J Pharmacol. 2009 May; 157(1):104-17.