LY-404187

LY-404187 is a potent, selective and centrally active positive allosteric modulator of AMPA receptors, with the EC₅₀s of 5.65, 0.15, 1.44, 1.66 and 0.21 µM for GluR1i, GluR2i, GluR2o, GluR3i and GluR4i, respectively. LY-404187 has therapeutic potential in a number of psychiatric disorders and neurodegenerative diseases^[1][2]. IC50 & Target: EC50: 5.65 µM (GluR1i), 0.15 µM (GluR2i), 1.44 µM (GluR2o), 1.66 µM (GluR3i), 0.21 µM (GluR4i)^[2] In Vitro: LY-404187 (3-10 nM) potentiates glutamate-evoked inward currents in human GluR4 transfected HEK293 cells^[2].
LY-404187 (0.03-10 µM) selectively enhances glutamate-evoked currents through AMPA receptor/channels of acutely isolated pyramidal neurons with considerably greater potency (EC₅₀=1.3±0.3 µM) and efficacy (E_max=45.3±8.0-fold increase) ^[3].
LY-404187 does not affect the magnitude or time course of wholecell K⁺ or Na⁺ currents in pre frontal cortex (PFC) pyramidal neurons at concentrations of 10 µM^[3]. In Vivo: LY-404187 (0.5 mg/kg; s.c for 11 days) can prevent MPTP-induced neurotoxicity in mice^[4].
LY-404187 (0.5 mg/kg; s.c. for 28 days) attenuates apomorphine-induced contraversive rotations and affords significant protection against the loss of tyrosine hydroxylase positive nigral cell bodies^[4].
LY-404187 (0.1 or 0.5 mg/kg; s.c. for 14 days) affords functional, neurochemical and histological protection after infusion of 6-hydroxydopamine into the substantia nigra in rats^[4].
LY-404187 (0.5 mg/kg; s.c. for 14 days) delayed treatment provides functional and histological improvement, suggesting a trophic action as administration is initiated after cell death^[4].
LY-404187 (0.1 and 0.5 mg/kg; s.c. for 14 days) increases GAP-43 immunoreactivity in the striatum in a dose-dependent manner^[4].