Org-26576 is a positive allosteric modulator of the AMPA receptor.

Org-26576 shows selectivity for AMPA receptors when tested at 10 μM against >60 molecular targets including G-Protein Coupled Receptors, ion channels, and kinases. Org-26576 represents structurally a distinct chemical series derived from the first generation ampakine CX516 and shows 10-30 fold greater potency when compared to CX516 in potentiating AMPA-mediated electrophysiological responses with an EC50 of 8-16 μM in rat hippocampal primary cultured neurons [1].

Org-26576 (Chronic administration) increases progenitor cell proliferation in the dentate gyrus (approximately 40%) and in the prelimbic cortex (approximately 35%) at the 10-mg/kg dosage. Cells born in response to chronic Org-26576 in dentate gyrus show increased rates of survival (approximately 30%) with the majority of surviving cells expressing a neuronal phenotype. Org-26576 (1 mg/kg) produces obviously enhances the anteroventral and laterodorsal thalamus, cingulate cortex, dentate gyrus, and CA3 subfield of the hippocampus in mice. AMPA receptor potentiation by Org-26576 exerts a positive modulatory influence on brain-derived neurotrophic factor (BDNF) expression during ongoing neuronal activity. Total BDNF mRNA levels are significantly increased in the hippocampus of animals exposed to the combination of Org-26576 and stress[1][2][3].