Irdabisant (CEP-26401) (CEP-26401) is a selective, orally active and blood-brain barrier (BBB) penetrant antagonist/inverse agonist of histamine H3 receptor (H3R) (rat H3R Ki= 7.2 nM, human H3R Ki= 2.0 nM). Irdabisant exhibits relatively low inhibitory activity against hERG current (IC50= 13.8 μM). Irdabisant exhibits cognition-enhancing and wake-promoting activities in the rat social recognition model. Irdabisant can be used for research on schizophrenia or cognitive impairment.

H3 receptor (rat):7.2 nM (Ki), H3 receptor (human):2 nM (Ki)

Irdabisant对大鼠H3R和人类H3R显示出逆激动剂活性，EC50值分别为2.0 nM和1.1 nM；对大鼠H3R和人类H3R展现出拮抗剂活性，Kb, app值分别为1.0 nM和0.4 nM。Irdabisant在胆碱能M2受体（Ki = 3.7 ± 0.0 μM）和肾上腺素α1A受体（Ki = 9.8 ± 0.3 μM），去甲肾上腺素转运体（Ki = 10 ± 1 μM），多巴胺转运体（Ki = 11 ± 2 μM）以及磷酸二酯酶PDE3（IC50 = 15 ± 1 μM）上表现出中等活性。Irdabisant抑制细胞色素P450酶CYP1A2、2C9、2C19、2D6和3A4，IC50值均大于30 μM，表明其化合物-化合物相互作用的潜力较低[1]。

Irdabisant（0.0001-0.1 mg/kg；静脉注射或口服；单剂量）在大鼠短期记忆的社交识别模型中提高了表现。Irdabisant（0.01-0.3 mg/kg；口服；单剂量）按剂量依赖方式抑制了H3R激动剂RAMH引起的口渴。Irdabisant（静脉注射1 mg/kg及口服3 mg/kg；单剂量）在大鼠和猴子中快速吸收，具有高口服生物利用度，并且与大鼠相比，在猴子和狗中展现了中等的清除率[1]。Irdabisant（3-30 mg/kg；口服；单剂量）在大鼠中表现出促进清醒的活动。Irdabisant（3-30 mg/kg；腹腔注射）在DBA/2NCrl小鼠中增加了前脉冲抑制（PPI）[2]。