L-838417

L-838417 is a selective partial agonist at the α2, α3 and α5 subtypes of the GABA_A receptor and an antagonist at the α1, with binding K_i values of 0.79 nM, 0.67 nM, 1.67 nM, 267 nM, 2.25 nM and 2183 nM for α1β3γ2, α2β3γ2, α3β3γ2, α4β3γ2, α5β3γ2 and α6β3γ2^[1]. IC50 & Target: Ki: 0.79 nM (α1β3γ2), 0.67 nM (α2β3γ2), 1.67 nM (α3β3γ2), 267 nM (α4β3γ2), 2.25 nM (α5β3γ2) and 2183 nM (α6β3γ2)^[1]. In Vivo: L-838417 (1.0 mg/kg) produces anxiolytic effects in adult rat, as indexed by a transformation of social avoidance into preference and an increase in social investigation^[2].
L-838417 (2.0 mg/kg) eliminates social avoidance, but has no anxiolytic effects on social investigation^[2].
L-838417 (0.5 mg/kg) reverses the anxiogenic effects of prior stress regardless of age, but with doses ≥ 1 mg/kg decreases social investigation, an effect possibly due in part to locomotor-impairing effects of this compound^[2].