L-838417

L-838417 is a selective partial agonist at the α2, α3 and α5 subtypes of the GABAA receptor and an antagonist at the α1, with binding Ki 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].

Signaling Pathways >> Membrane Transporter/Ion Channel >> GABA Receptor

Research Areas >> Neurological Disease

Signaling Pathways >> Neuronal Signaling >> GABA Receptor

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].

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]. Animal Model: Male and female adolescent and adult Sprague–Dawley rats[2]. Dosage: 0, 0.5, 1.0, 2.0, or 4.0 mg/kg. Administration: IP. Result: Adolescents required a higher dose (2 mg/kg) to attenuate their social avoidance. The lowest dose of 0.5 mg/kg was sufficient to reverse the anxiogenic effects of repeated restraint as reflected by a significant increase in the coefficient relative to vehicle-treated animals.

[1]. Ciara McCabe, et al. Subtype-selective GABAergic drugs facilitate extinction of mouse operant behavior. Neuropharmacology. 2004 Feb;46(2):171-8.

[2]. Melissa Morales, et al. Anxiolytic effects of the GABAA receptor partial agonist, L-838,417: Impact of age, test context familiarity, and stress. Pharmacol Biochem Behav. 2013 Aug;109:31-7.