GSK189254A (hydrochloride)

GSK189254A hydrochloride is a novel, potent and selective histamine H3 receptor antagonist with pK_i values of 9.59-9.90 and 8.51-9.17 for human and rat H3, respectively^[1]. IC50 & Target:pKi: 9.59-9.90 (H3, human), 8.51-9.17 (H3, rat)^[1] In Vitro:GSK189254A hydrochloride 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. GSK189254A hydrochloride generally exhibits higher affinity for human and pig H3 receptors compared with rat,mouse, and dog H3 receptors. [³H] GSK189254A hydrochloride binds in rat and human brain areas, including cortex and hippocampus. GSK189254A hydrochloride may have therapeutic potential for the symptomatic treatment of dementia in Alzheimer’s disease and other cognitive disorders ^[1]. In Vivo:GSK189254A hydrochloride (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. GSK189254A hydrochloride 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 GSK189254A hydrochloride increases W and decreases slow wave and paradoxical sleep to a similar degree to modafinil, while it reduces narcoleptic episodes in Ox−/− mice^[2].