GSK189254A (GSK189254) is a potent and specific histamine H3 receptor antagonist (pKi values: 9.59-9.90 and 8.51-9.17 for human and rat H3).

H3 receptor (human):9.59-9.90 (pKi), H3 receptor (mouse):8.51-9.17 (pKi)

GSK189254 对于在HEK-293-MSR-II细胞中表达的重组H3受体以及多种物种大脑皮层中表达的天然H3受体均具有高亲和力。GSK189254 通常对人类和猪的H3受体展现出更高的亲和力，相比之下，与小鼠、大鼠和狗的H3受体的亲和力较低。GSK189254 可能对阿尔茨海默病和其他认知障碍的症状性治疗具有潜在的治疗价值[1]。

在Ox+/+和Ox/小鼠中，GSK189254的急性给药能够增加W，降低慢波睡眠和反常睡眠的程度，与modafinil相似，同时在Ox/小鼠中减少了发作的纳尔科病次数[2]。GSK189254（0.3-3 mg/kg p.o.）增加了前扣带皮质中乙酰胆碱、去甲肾上腺素和多巴胺的释放，以及在背侧海马中的乙酰胆碱释放。GSK189254显著提高了在多种认知范式中大鼠的表现，包括被动避免、水迷宫、物体识别和注意集合转移[1]。

Pharmacokinetic studies with GSK189254 are conducted in conscious male Sprague-Dawley rats. Animals receive an intravenous infusion of GSK189254 (n=3) administered at a nominal dose level of 1 mg of free base/kg for 1 h via the femoral vein cannula (10 mL/h/kg). GSK189254 is dissolved in 0.9% (w/v) saline at a target concentration of 0.1 mg free base/mL and filtered with a 0.22-mm Millex-GV filter before administration. After an ish out of at least 2 days, the same rats received a single oral administration of GSK189254 by gastric gavage to achieve a target dose of 2 mg of free base/kg. GSK189254 is formulated in 1% (w/v) aqueous methylcellulose at a target concentration of 0.4 mg free base/mL [1]. The vehicle consists of 0.05 mL NaCl at 0.9% containing methylcellulose at 1%. GSK189254 is a dissolved in-vehicle solution. The effects of acute and repeat administration of GSK189254 on the sleep-wake cycle in wild-type (Ox+/+) and orexin knockout (Ox?/?) mice is investigated. GSK189254 (3 and 10 mg/kg, p.o.) is administered on the sleep-wake cycle in Ox+/+ and Ox?/? mice, dosed at 10 h. The oral administration dose of GSK189254 is 10 mg/kg [2].