Irdabisant

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Irdabisant (CEP-26401) 是一种具有选择性、口服活性和血脑屏障渗透性的组胺 H3 受体 (histamine H3 receptor, H3R) 拮抗剂/逆激动剂，对大鼠 H3R 和人 H3R 的 Ki 分别为 7.2 nM 和 2.0 nM。Irdabisant 对 hERG 电流的抑制活性相对较低，IC50 为 13.8 μM。Irdabisant 在大鼠社会认知模型中具有认知增强和唤醒作用。Irdabisant 可用于精神分裂症或认知障碍的研究。

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

Irdabisant (CEP-26401, compound 8a) shows antagonist activity with Kb, app values of 1.0 nM and 0.4 nM for rat H3R and human H3R, respectively; shows inverse agonist activity with EC50 values of 2.0 nM and 1.1 nM for rat H3R and human H3R, respectively.Irdabisant has moderate activity at Muscarinic M2 (Ki = 3.7 ± 0.0 μM) and Adrenergic α1A (Ki = 9.8 ± 0.3 μM) receptors, Dopamine transporters (Ki = 11 ± 2 μM), Norepinephrine transporters (Ki = 10 ± 1 μM), and phosphodiesterase PDE3 (IC50 = 15 ± 1 μM).Irdabisant inhibits the cytochrome P450 enzymes CYP1A2, 2C9, 2C19, 2D6, and 3A4 with IC50 values of greater than 30 μM, indicating less potential for drug-drug interactions.

CEP-26401 (0.01-0.3 mg/kg; p.o.; single dosage) dose-dependently inhibits H3R agonist RAMH-induced dipsogenia.CEP-26401 (0.0001-0.1 mg/kg; i.v. or p.o.; single dosage) improves performance in the rat social recognition model of short-term memory.CEP-26401 (3-30 mg/kg; p.o.; single dosage) exhibits wake-promoting activity in rat.CEP-26401 (3-30 mg/kg; i.p.) increases prepulse inhibition (PPI) in DBA/2NCrl mice.CEP-26401 (1 mg/kg for i.v. and 3 mg/kg for p.o.; single dosage) is rapidly absorbed with high oral bioavailability in rat and monkey, and shows a moderate clearance in monkey and dog compared to the rat. Pharmacokinetic Parameters of Irdabisant (compound 8a) in rats, dogs and monkeys.Animal Model:Male Sprague-Dawley rats (i.p. 10 mg/kg RAMH-induced dipsogenia model) Dosage:0.01-0.3 mg/kg Administration: p.o.; single dosage Result:Dose-dependently inhibited H3R agonist RAMH (HY-100999)-induced dipsogenia (which manifests as water drinking) with an EC50 value of 0.06 mg/kg.Animal Model:Male Sprague-Dawley rats (adult rats were briefly exposed to a juvenile rat for build social recognition model)Dosage:0.0001, 0.001, 0.01 and 0.1 mg/kg for i.p.; 0.01 and 0.1 mg/kg for p.o.Administration:i.v. or p.o.; single dosage Result:Effectively reduced the ratio of investigation duration (RID) at doses over the range from 0.001 to 0.1 mg/kg i.p. and at 0.01 and 0.1 mg/kg p.o., demonstrating potent enhancement of short-term sensory memory in this model.Animal Model:Male Sprague-Dawley rats Dosage:3, 10 and 30 mg/kg Administration:p.o.; single dosageResult:Exhibited robust wake promotion with the treated animals awake 90% of the time up to 3 h postdosing at 30 mg/kg.

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GPCR/G Protein

Histamine Receptor

Histamine Receptor

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1005402-19-6

313.39

C18H23N3O2

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 50 mg/mL (159.55 mM; 超声助溶 (<60°C)

O(CCCN1[C@H](C)CCC1)C2=CC=C(C=C2)C=3C=CC(=O)NN3

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(-20℃)

With Ice Pack

≥ 2 years