GSK189254A (GSK189254) 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.
GSK189254 has high affinity for both recombinant H3 receptors expressed in HEK-293-MSR-II cells and native H3 receptors expressed in the cerebral cortex of several species. GSK189254 generally exhibits higher affinity for human and pig H3 receptors compared with rat,mouse, and dog H3 receptors. [3H]GSK189254 binds 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 [1].
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].
References:
[1]. Medhurst AD, et al. GSK189254, a novel H3 receptor antagonist that binds to histamine H3 receptors in Alzheimer's disease brain and improves cognitive performance in preclinical models. J Pharmacol Exp Ther. 2007 Jun;321(3):1032-45.
[2]. Guo RX, et al. Differential effects of acute and repeat dosing with the H3 antagonist GSK189254 on the sleep-wake cycle and narcoleptic episodes in Ox-/- mice.Br J Pharmacol. 2009 May;157(1):104-17.