211311-95-4

LY404187 is a benzothiadiazide positive allosteric modulator of AMPA receptors. It increases glutamate-induced activation of GluR1_i, -2_i, -2_o, -3_i, and -4_i subunit-containing AMPA receptors with EC₅₀ values of 5.65, 0.15, 1.44, 1.66, and 0.21 μM, respectively, in a calcium influx assay. LY404187 is selective for these AMPA receptors over GluR6 subunit-containing kainate receptors at 10 μM. LY404187 increases currents induced by glutamate and AMPA in rat prefrontal cortex pyramidal neurons (EC₅₀s = 1.3 and 1.2 μM, respectively) but not in AMPA-stimulated primary rat embryonic hippocampal or primary cerebellar Purkinje neurons. LY404187 prevents decreases in the number of dopaminergic neurons in the substantia nigra induced by MPTP and 6-OHDA in mouse and rat, respectively, models of Parkinson’s disease when administered at a dose of 0.5 mg/kg per day.

LY 404187 is a novel positive allosteric modulator of AMPA receptors.

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