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 www.vistagen.com
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