Basmisanil

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

GABAA 受体 α5 亚型的新型选择性负变构调节剂。

A novel selective negative allosteric modulator of the GABAA receptor α5-subtype, which is under development for the treatment of cognitive impairment associated with Down syndrome.Schizophrenia Phase 2 Clinical(In Vitro):Basmisanil (0.1 nM-100 μM) has high affinity for bounding to recombinant human GABAA-α5 receptors with a Ki value of 5 nM and more than 90-fold selectivity versus α1 (Ki = 1031 nM), α2 (Ki = 458 nM), and α3 (Ki = 510 nM) subunit-containing receptors.Basmisanil (1 nM-1 μM) shows a highly selective inhibition of GABAA-α5 with a IC50 value of 8 nM.Basmisanil (1 μM) inhibits GABA-induced currents at GABAA-α5 yet had little or no effect at the other receptor subtypes.(In Vivo):Basmisanil (3-100 mg/kg, p.o.) occupies GABAA-α receptor in dose-dependent in rat brain.Basmisanil (3-600 mg/kg p.o.) improves cognition in rats and non.human primates and not show anxiogenic or proconvulsant effects.

Basmisanil (0.1 nM-100 μM) has high affinity for bounding to recombinant human GABAA-α5 receptors with a Ki value of 5 nM and more than 90-fold selectivity versus α1 (Ki = 1031 nM), α2 (Ki = 458 nM), and α3 (Ki = 510 nM) subunit-containing receptors.Basmisanil (1 nM-1 μM) shows a highly selective inhibition of GABAA-α5 with a IC50 value of 8 nM.Basmisanil (1 μM) inhibits GABA-induced currents at GABAA-α5 yet had little or no effect at the other receptor subtypes.

Basmisanil (3-100 mg/kg, p.o.) occupies GABAA-α receptor in dose-dependent in rat brain.Basmisanil (3-600 mg/kg p.o.) improves cognition in rats and non.human primates and not show anxiogenic or proconvulsant effects. Animal Model:Sprague Dawley rats(180 g; female).Dosage:3-100 mg/kgAdministration:p.o.Result:Decreased the binding of [3H]-Ro 15-4513 in a dose-dependent manner.Reduced specific binding in the hippocampus by 70% at the highest dose (100 mg/kg).Animal Model:Lister Hooded rats, Wistar rats and F-344 Fischer rats (Lister Hooded rats: 220-250 g; male)(Wistar rats: 200-220 g; male and female) (F-344 Fischer rats: 170-180 g; male)Dosage:3-600 mg/kg Administration:p.o.Result:Significantly attenuated the diazepam-induced deficit.Showed plasma concentrations in dose- and time-dependent manner and reached a maximal level of 903 ng/mL (379 nM free plasma) 30 min after the administration at 10 mg/kg.Animal Model:Male cynomolgus macaques(Macaca fascicularis; 7-10 kg)Dosage:1-600 mg/kg Administration:p.o.Result:Significantly improved the percentage of correct first reaches during difficult trials of the object retrieval task at the 3 and 10 mg/kg doses.Exhibited an inverted U-shaped dose response in this paradigm with the 1 and 30 mg/kg doses producing no marked improvement on performance.Increased the total plasma exposure in dose-dependent.

RG-1662 | RO5-186582

Membrane Transporter/Ion Channel

GAT

GAT

Neurological Disease

Schizophrenia

1159600-41-5

445.464

C21H20FN3O5S

>98% (HPLC)

DMSO: ≥ 32 mg/mL

O=C(N1CCS(CC1)(=O)=O)C2=CC=C(OCC3=C(C)ON=C3C4=CC=C(F)C=C4)N=C2

Methanone, (1,1-dioxido-4-thiomorpholinyl)[6-[[3-(4-fluorophenyl)-5-methyl-4-isoxazolyl]methoxy]-3-pyridinyl]-

(-20℃)

With Ice Pack

≥ 2 years