Antidepressants are the most commonly consumed class of therapeutics in the United States, prescribed to more than 270 million patients each year. Ketamine, an NMDA receptor antagonist used as an anesthetic in human and veterinary medicine, can also be effective in treating depression. The drug's side effects, such as hallucinations or psychotic symptoms, however, have made it a widely used and dangerous recreational drug referred to as "Special K."
The hallucinogenic and psychotic side effects hinder the interpretation of its clinical activity and limit its use as a therapeutic option for many patients. As the dangers of mental illness becomes more and more evident in our society, researchers are racing to find an adequate antidepressant alternative without the psychotic adverse effects.
According to a recent article in the Nature Reviews research journal, scientists have done just that. Monica Hoyos Flight's article, "Phase 2 boost for glutamate-targeted antidepressants," discusses the results of a phase 2 trial that suggest lanicemine as an alternative antidepressant with minimal adverse psychotomimetic effects. Flight also names several NMDA receptor blocking agents, including VistaGen Therapeutic's AV-101.
Scientists at Yale University in collaboration with AstraZeneca conducted a trial to study 152 patients with moderate-to-severe depression and a weak response to antidepressants. Like ketamine, lancemine showed efficacy as an NMDA receptor antagonist, a key feature in bringing relief of depressive symptoms. Results showed a significant improvement in the level of depression in patients administered lanicemine vs. placebo, without hallucinations or psychotic symptoms.
But for lanicemine to gain approval and clinical acceptance, it must demonstrate robust effects comparable to ketamine, provide rapid onset relief, and have a toxicology profile that shows safety if the drug is taken daily.
"The race is on to introduce safe and effective rapidly acting antidepressants for the most seriously ill mood disorder patients," Flight quotes Sanjay J. Mathew, at the Michael E. Debakey VA Medical Center in Houston, Texas, as saying. "There are multiple such agents in early phases of development, including S-ketamine (the S-isomer of the racemic ketamine), GLYX-13 (a partial NMDA receptor agonist) and AV-101, a selective blocker of the regulatory GlyB site of the NMDA receptor."
AV-101 is VistaGen's lead small molecule drug candidate, which has successfully completed phase 1 development in the U.S. for the treatment of neuropathic pain. The company has been awarded more than $8.8 million from the Nation Institute of Health for further development of AV-101, and VistaGen believes that its phase 1 safety program will enable phase 2 development of the drug candidate for neuropathic pain, other neurological conditions and depression.
With researchers and scientists from some of the nation's leading academic institutions conducting studies for the highly sought discovery of an alternative to ketamine for the treatment of depression, VistaGen has positioned itself for potential among the ranks of leading candidates.
For more information, visit vistagen.com
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