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Drug Development
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AV-101 for Epilepsy
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Orally Available Prodrug with Breakthrough Potential & Improved Side-Effect
Profile
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Mechanism
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VistaGen's AV-101
(L-4-chlorokynurenine) is a novel, orally available prodrug that is
converted in the brain into an active metabolite, 7-chlorokynurenic acid
(7-CKYNA). 7-CKYNA is a synthetic analogue of kynurenic acid--a naturally
occurring regulatory neuroinhibitory compound--and is one of the most potent
GlyB receptor antagonists known. In
preclinical studies, VistaGen’s AV-101 has greater than 90% oral bio
availability, is rapidly and efficiently transported across the blood-brain
barrier, and is converted into 7-CKYNA in the brain and spinal cord
preferentially at the site of potential neural damage.
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Efficacy & Safety
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| AV-101 regulates NMDA-receptor function in the brain controlling excessive pathological signaling, such as occurs during epilepsy, while allowing the normal activation of these receptors to occur when the brain transmits signals or forms a memory. Active metabolite of AV-101 is an analogue of a naturally occurring neuroregulator produced in the brain.
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| AV-101 reduces the frequency and duration of seizures in two key animal models of human epilepsy.
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| AV-101 has been shown to be converted, at high efficiency, into the active metabolite in human “epileptic” brain tissue samples.
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| Preclinical studies demonstrate AV-101 to be very powerful in preventing the brain damage induced by excessive activation of NMDA-receptors. This effect is mediated not only by regulating the NMDA-receptor, but also by inhibiting the production of the neurotoxic quinolinic acid, which is produced in the brain during convulsions and neurodegenerative processes. The synthesis of quinolinic acid is inhibited by a metabolytic breakdown product of 7-CKYNA.
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| Preferential production of the active metabolite of AV-101 at the site of action in the brain is expected to allow a reduction of the blood drug concentration while maintaining high therapeutic levels at the site of action.
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| GlyB receptor antagonists tested in humans for treating stroke have demonstrated good safety profiles. |
Development Timeline
VistaGen is currently completing preclinical development of AV-101, and
expects to file INDs for epilepsy and neuropathic pain in late 2007.
For more information about Epilepsy, right mouse click
here
to download video.
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