Potential Breakthrough in Depression Treatment

Potential for Ketamine-like Antidepressant Effects without Ketamine's CNS Side-Effects

AV-101 (L-4-chlorokyurenine or 4-CI-KYN) is an orally available new generation prodrug candidate, in Phase 2 development, initially for the adjunctive treatment of major depressive disorder (MDD) in patients with an inadequate response to standard antidepressants.

VistaGen believes it has the potential to expand AV-101 into multiple additional CNS indications beyond adjunctive treatment of MDD, including neuropsychiatric disorders (depression and bipolar depression), neurological disorders (chronic neuropathic pain and epilepsy) and neurodegenerative disorders (Huntington's disease and Parkinson's disease), each representing potential blockbuster opportunities.

  • New generation oral antidepressant prodrug candidate, rapidly absorbed through the gut, actively transported into the brain, converted into its active metabolite, 7-Cl-KYNA, and binds to NMDAR GlyB site
  • Similar to ketamine: acts in the brain through the same glutamatergic AMPA-dependent pathway, rapidly inducing antidepressant effects
  • Safer than ketamine: blocks the NMDAR through GlyB site binding; ketamine blocks the ion channel of NMDARs, causing its negative side effects
  • Safe and well-tolerated in two NIH-funded Phase 1 safety studies; no ketamine-like side effects
  • Drug-drug interaction and "Black Box" metabolic effects related to standard antidepressants and atypical antipsychotics not anticipated

AV-101 Mechanism of Action Video

AV-101's Metabolite (7-Cl-KYNA) Inhibits NMDA Receptor Activity

In peer-reviewed and published preclinical studies, AV-101 demonstrated the robust antidepressant-like activity of the NMDA receptor antagonist ketamine HCl, an FDA-approved anesthetic, including low dose ketamine's rapid onset and long duration of antidepressant effects, without any of ketamine's CNS side effects. In two NIH-funded randomized, double-blind, placebo-controlled Phase 1 safety studies, AV-101 was safe, well-tolerated and not associated with any severe adverse events. There were no signs of sedation, hallucinations or schizophrenia-like side effects often associated with ketamine and other NMDA receptor ion channel blockers.

AV-101's Mechanism is Fundamentally Differentiated from All FDA-Approved Standard Antidepressants and Atypical Antipsychotics