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VistaGen Therapeutics, Inc. (VSTA) Sees AV-101 as Potential Breakthrough Drug for Major Depressive Disorder

Potential to Address Major U.S. and Global Need

It’s one of the single most sought-after drugs in the medical industry, and biotechnology company VistaGen Therapeutics may have it. What is so desperately needed is a drug able to treat a disease that afflicts tens of millions of people in the U.S., and hundreds of millions globally. The disease is MDD (Major Depressive Disorder), a crippling form of depression that is not effectively treated by existing medications. It is now recognized as a disease that seriously undermines economies and society as a whole, contributing to hundreds of thousands of deaths worldwide each year. The recent death of actor and comedian Robin Williams has shed a public light on the gravity of individual depression, but researchers know that it affects as many as one out of 20 households. They also know the significant issues with standard treatments for MDD.

Current Drugs Too Slow or With Side Effects

Traditional FDA-approved drugs currently used to treat depression are very slow acting, a consequence of the way they operate in the brain. It can take weeks or even months to achieve the intended benefit of these antidepressants, time that patients experiencing an MDD crisis often don’t have. The lack of noticeable and timely results with such treatments can easily discourage people with MDD from continuing with their antidepressant medications. In desperation a patient can slide from one drug to another until they feel they’ve run out of options, potentially with fatal results.

So anxious is the medical establishment for an effective quick-acting anti-depressant that ketamine, a multi-purpose pain killer and anesthetic, has been re-purposed by certain physicians as an anti-depressant, primarily because of its ability to deliver rapid, robust antidepressant effects in MDD patients. An article in Scientific American ( talked about how the ketamine’s promise has ignited excitement among clinicians and neuroscientists, in spite of its associated adverse effects, pointing out that “a person taking ketamine may experience altered physical, spatial and temporal states; larger quantities may induce hallucinations and dissolution of the self”. Over and above what an article in Nature Reviews ( called “psychosis-like side effects”, another major problem with ketamine is that it must be given intravenously. Forcing patients to get frequent infusions to stave off depression is nobody’s idea of an optimum solution, but it underscores the serious, unmet medical need in this area.

New Drug May Be Perfect Storm

Amidst all of this has come a highly innovative new approach from California-based VistaGen Therapeutics, a biopharmaceutical company known primarily for its stem cell technology. VistaGen’s novel, orally available MDD drug candidate AV-101 is ready for Phase 2 clinical development in the U.S. and is starting to look like a very big deal, because it offers the promise of being an antidepressant that is both powerful and quick-acting, while at the same time causing none of the mind-bending side effects of ketamine. The drug operates in a different way than the other FDA-approved antidepressant drugs, providing a much more moderated effect while still getting the job done. NIH sponsored Phase 1 studies of AV-101 have already shown it to be a remarkably safe and well-tolerated compound. Perhaps even more notable is the fact that AV-101 can be taken orally, with no need for regular injections or IV administration. It’s an almost ideal combination of properties, with a multi-billion dollar market on the table.

From a technical standpoint, AV-101 (4-Cl-KYN) is an orally-available, non-sedating, non-hallucinogenic prodrug (precursor drug) that is rapidly and enzymatically converted to its active metabolite, 7-chlorokynurenic acid (7-Cl-KYNA), one of the most well-characterized, potent, and selective synthetic blockers of N-methyl-D-aspartate (NMDA) receptors at the glycine-coagonist (GlyB) site. Although the pathophysiology of depression has been linked to monoaminergic mechanisms for decades, compelling evidence now suggests a key role of the glutamatergic system in mood disorders and favors the idea that AV-101’s targeted antagonism of the glycineB site of the NMDA receptor can provide rapid, robust antidepressant effects in treatment of MDD similar to ketamine, but without ketamine’s serious side effects.

VistaGen is currently preparing for a Phase 2 MDD study in early 2015, so keep an eye open for announcements.

In addition to MDD, AV-101 is now also being seen as a potential treatment for other diseases involving the central nervous system, including epilepsy, chronic neuropathic pain, and neurodegenerative disorders such as Parkinson’s disease.

For additional information, visit the company’s website at

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