Nemorexant (ACT-541468), a benzimidazole derivative, is an orally selective dual-orexin antagonist (DORA) [1]. Nemorexant can cross the blood-brain-barrier (BBB) and work by competitively binding to the active site of orexin 1 and orexin 2 receptors[2]. Nemorexant has been widely used to reduce the arousal state and promote sleep in animals, and to maintain overall sleep architecture[3].
In vivo, Nemorexant treatment via oral administration at a dose of 200mg/kg/day for 14 days reduced the body temperature of the rats, resulting in decreased locomotor activity and a lower level of vertical activity[4]. Oral administration of Nemorexant (100mg/kg/day) for three consecutive days prior to lipopolysaccharide (LPS) injection enhanced rapid eye‐movement (REM) sleep recovery, and decreased the expression of proinflammatory cytokines (Cxcl1, Ccl2, Ccl7, and Tnf) in the hypothalamus in the LPS-induced systemic inflammation model[5].
References:
[1] Ziemichód W, Grabowska K, Kurowska A, et al. A comprehensive review of daridorexant, a dual-orexin receptor antagonist as new approach for the treatment of insomnia[J]. Molecules, 2022, 27(18): 6041.
[2] Robinson C L, Supra R, Downs E, et al. Daridorexant for the Treatment of Insomnia[J]. Health psychology research, 2022, 10(3): 37400.
[3] Roch C, Bergamini G, Steiner M A, et al. Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia[J]. Psychopharmacology, 2021, 238(10): 2693-2708.
[4] Steiner M A, Toeroek-Schafroth M, Giusepponi M E, et al. Abuse potential assessment of the dual orexin receptor antagonist daridorexant in rats[J]. Journal of Psychopharmacology, 2023, 37(12): 1249-1260.
[5] Horiuchi D, Irukayama‐Tomobe Y, Kim J D, et al. Orexin Receptor Antagonism Improves Sleep Quality and Mitigates Lipopolysaccharide‐Induced Inflammatory Responses in a Mouse Model[J]. The FASEB Journal, 2026, 40(1): e71408.
Nemorexant (ACT-541468)是一种苯并咪唑衍生物，是一种口服选择性双重orexin受体拮抗剂（DORA）[1]。Nemorexant可穿过血脑屏障（BBB），通过竞争性结合orexin 1和orexin 2受体的活性位点发挥作用[2]。Nemorexant已被广泛用于降低动物的觉醒状态、促进睡眠，并维持整体的睡眠结构[3]。
在体内，每日口服给予200mg/kg剂量的Nemorexant，持续14天，降低了大鼠的体温，导致自主活动减少和垂直活动水平降低[4]。在脂多糖（LPS）注射前连续三天口服给予Nemorexant（100mg/kg/day），在LPS诱导的全身炎症模型中，增强了快速眼动（REM）睡眠的恢复，并降低了下丘脑中促炎细胞因子（Cxcl1、Ccl2、Ccl7和Tnf）的表达[5]。