Basmisanil

SKU: orb1226895

Description

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.

Key Properties

• CAS Number: 1159600-41-5
• MW: 445.464
• Purity: >98% (HPLC)
• Formula: C₂₁H₂₀FN₃O₅S
• SMILES: O=C(N1CCS(CC1)(=O)=O)C2=CC=C(OCC3=C(C)ON=C3C4=CC=C(F)C=C4)N=C2
• Target: GAT
• Solubility: DMSO: ≥ 32 mg/mL

Bioactivity

• 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. Animal model: Sprague Dawley rats(180 g; female). Dosage: 3-100 mg/kg. Administration: 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.
• 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

RG-1662 | RO5-186582

Quick Database Links

Gene Symbol

GAT