ONO-8590580

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

ONO-8590580 是一种新型有效的选择性 GABAA α5 负变构调节剂。

ONO-8590580 is a novel potent, selective GABAA α5 negative allosteric modulator, binds to the benzodiazepine binding sites on recombinant human α5-containing GABAA receptors with Ki of 7.9 nM; shows functionally selective GABAA α5 NAM activity for GABA-induced Cl- channel activity with a maximum 44.4% inhibition and an EC50 of 1.1 nM; significantly augments tetanus-induced long-term potentiation of CA1 synapse response in rat hippocampal slices at 300 nM; significantly prevents MK-801-induced memory deficit in vivo (3-20 mg/kg, p.o.).

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The effect of ONO-8590580 on the MK-801/scopolamine-induced cognitive deficit in the 8-arm radial maze test is investigated. Doses of MK-801 and scopolamine for this test are 0.075 mg/kg (i.p.) and 0.2 mg/kg (i.p.) respectively. ONO-8590580 (20 mg/kg, p.o.) significantly decreases the number of errors and total latency compared to the control. The present study in which ONO-8590580 but not donepezil significantly decreases the number of errors may suggest that ONO-8590580 could be more potent for the treatment of AD patients. The data showing that ONO-8590580 has not anxiogenic-like or proconvulsant effects are in agreement with the behavioral phenotype of α5-/- mice.

ONO8590580

Membrane Transporter/Ion Channel

GAT

GAT

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1802661-73-9

376.439

C21H21FN6

>98% (HPLC)

DMSO : 62.5 mg/mL 166.03 mM

CN1C=C(C2=CN=C(NC3=C(F)C(C)=C4C(N(CC5CC5)C=N4)=C3)C=C2)N=C1

1-(cyclopropylmethyl)-5-fluoro-4-methyl-N-[5-(1-methyl-1H-imidazol-4-yl)-2-pyridinyl]-1H-benzimidazol-6-amine

(-20℃)

With Ice Pack

≥ 2 years