A ligand for α5 subunit-containing GABAA receptors with nootropic activity
L-655708 is a potent α5 subunit-selective GABAA receptor inverse agonist (Ki = 0.45 nM).IC50: 0.45 nM (Ki)Target: GABAin vitro: L-655708 is a potent, selective inverse agonist for the benzodiazepine site of GABAA receptors containing the α5 subunit (Ki = 0.45 nM). Displays 50-100-fold selectivity over GABAA receptors containing α1, α2, α3 orα6 subunits in combination with β3 and γ2. Enhances LTP in a mouse hippocampal slice model and increases spatial learning, without displaying proconvulsant activity.in vivo: L-655708 at 0.7 mg/kg, administered intraperitoneally, would result in 60-70% occupancy of α5 GABAA receptors with limited binding to α1, α2, and α3 subunit-containing GABAA receptors and no significant off-target behavioral effects, such as sedation and motor impairment.[1]
参考文献:
[1]. Saab BJ, et al. Short-term memory impairment after isoflurane in mice is prevented by the α5 γ-aminobutyric acid type A receptorinverse agonist L-655708. Anesthesiology. 2010 Nov;113(5):1061-1071.
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