ONO-8590580

ONO-8590580 is a negative allosteric modulator of alpha5 subunit-containing GABAA receptors that binds at the benzodiazepine binding site. It binds to alpha1, alpha2, alpha3, and alpha5 subunit-containing GABAA receptors (Kis = 140, 32, 24, and 7.9 nM, respectively). It is selective for inhibiting GABA-induced currents in HEK293 cells expressing human recombinant alpha5beta3gamma2 subunits (EC50 = 1.1 nM) over those expressing human recombinant alpha1beta3gamma2, alpha2beta3gamma2, or alpha3beta3gamma2 subunits for which it has little to no activity. ONO-8590580 (300 nM) enhances long-term potentiation in rat hippocampal brain slices. It decreases MK-801-induced memory deficits in the rat passive avoidance test when administered at doses ranging from 3 to 20 mg/kg. ONO-8590580 (20 mg/kg, p.o.) decreases MK-801- and scopolamine-induced increases in the latency to complete, and the number of errors made in, the eight-arm radial maze test in rats. It does not induce anxiety-like or proconvulsant behavior in rats in the elevated zero maze or pentylenetetrazole-induced seizure test when administered at a dose of 20 mg/kg.Formal Name: 1-(cyclopropylmethyl)-5-fluoro-4-methyl-N-[5-(1-methyl-1H-imidazol-4-yl)-2-pyridinyl]-1H-benzimidazol-6-amine. CAS Number: 1802661-73-9. Molecular Formula: C21H21FN6. Formula Weight: 376.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: soluble. lambdamax: 266, 290, 320 nm. SMILES: FC1=C(NC2=CC=C(C3=CN(C)C=N3)C=N2)C=C4C(N=CN4CC5CC5)=C1C. InChi Code: InChI=1S/C21H21FN6/c1-13-20(22)16(7-18-21(13)25-12-28(18)9-14-3-4-14)26-19-6-5-15(8-23-19)17-10-27(2)11-24-17/h5-8,10-12,14H,3-4,9H2,1-2H3,(H,23,26). InChi Key: INGJMHPGMVUEKY-UHFFFAOYSA-N.