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VistaGen Therapeutics Announces Positive Preclinical Data of AV-101 Combined with Probenecid Suggesting Substantially Increased Brain Concentration Effects
When given together with VistaGen's oral prodrug AV-101, probenecid increased brain concentrations of AV-101 7-fold and its active metabolite, 7-CI-KYNA,
About this update from Vistagen Therapeutics, Inc.
[{"type":"text","content":"When given together with VistaGen's oral prodrug AV-101, probenecid increased brain concentrations of AV-101 7-fold and its active metabolite, 7-CI-KYNA, 35-fold\n\n\nSOUTH SAN FRANCISCO, Calif., Feb. 11, 2020 /PRNewswire/ -- VistaGen Therapeutics (NASDAQ: VTGN), a clinical-stage biopharmaceutical company developing new generation medicines for central nervous system (CNS) diseases and disorders with high unmet medical need, today announced positive preclinical data of AV-101, an oral NMDAR (N-methyl-D-aspartate receptor) antagonist prodrug, administered in combination with probenecid. The new preclinical data suggest that there is a substantially increased brain concentration of AV-101 and its active metabolite, 7-chlorokynurenic acid (7-Cl-KYNA), when given together with probenecid. These surprising effects were first revealed in the Company's recent preclinical study, although they are consistent with well-documented clinical studies of probenecid increasing the therapeutic levels of several unrelated classes of approved drugs.\n\n \n \n\n \n\"The remarkable preclinical data announced today demonstrate a 7-fold concentration increase in the brain of AV-101 prodrug, and, more importantly, a 35-fold increase of 7-Cl-KYNA, AV-101's active metabolite, when AV-101 is administered adjunctively with probenecid. We recently identified that some of the same kidney transporters that reduce drug concentrations in the blood, by excretion in the urine, are also found in the blood brain barrier and function to reduce 7-Cl-KYNA levels in the brain by pumping it out of the brain and back into the blood. In the recent studies, we discovered that blocking those transporters in the blood brain barrier with probenecid resulted in a substantially increased brain concentration of 7-Cl-KYNA,\" said Ralph Snodgrass, Ph.D., President and Chief Scientific Officer of VistaGen. \"This 7-Cl-KYNA efflux-blocking effect of probenecid, with the resulting increased brain levels and duration of 7-Cl-KYNA, suggests the potential impact of AV-101 with probenecid could result in far more profound therapeutic benefits for patients with major depressive disorder and other NMDAR-focused CNS diseases and disorders than demonstrated in the Phase 2 studies of AV-101 in major depressive disorder completed last year,\" added Dr. Snodgrass. \nResults on AV-101 transport ...