ORG-26576; ORG26576; ORG 26576

Org-26576 (Org 26576) represents structurally a distinct chemical series derived from the first generation ampakine CX516 and displays 10-30 fold greater potency when compared to CX516 in potentiating AMPA-mediated electrophysiological responses with an EC ₅₀ of 8-16 μM in rat hippocampal primary cultured neurons. Org-26576 demonstrates selectivity for AMPA receptors when tested at 10 μM against >60 molecular targets including G-Protein Coupled Receptors, ion channels and kinases.

Org-26576 (Org 26576; 1 mg/kg) produces significant increases in the anteroventral and laterodorsal thalamus, cingulate cortex, dentate gyrus and CA3 subfield of the hippocampus in mice. Chronic administration of Org-26576 (Org 26576) increases progenitor cell proliferation in dentate gyrus (approximately 40%) and in prelimbic cortex (approximately 35%) at the 10-mg/kg dosage. Cells born in response to chronic Org-26576 in dentate gyrus exhibits increased rates of survival (approximately 30%) with the majority of surviving cells expressing a neuronal phenotype. AMPA receptor potentiation by Org-26576 (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.