N-methyl-D-aspartate (NMDA) glutamate receptor antagonists are used in clinical anesthesia and are being developed as therapeutic agents for preventing neurodegeneration in stroke, epilepsy, and brain trauma. However, the ability of these agents to produce neurotoxicity in adult rats and psychosis in adult humans compromises their clinical usefulness. In addition, an NMDA receptor hypofunction (NRHypo) state might play a role in neurodegenerative and psychotic disorders, like Alzheimer’s disease, bipolar disorder and schizophrenia.
In addition to the glutamate (NMDA) binding site, there are also multiple binding sites on the NMDA receptor for modulatory compounds. Efficient NMDA receptor activation requires not only NMDA but also a co-agonist, glycine.
I have been using a combination of L-Glycine & L-Glutamine (converts to glutamic acid) co-administered with lamictal for the treatment of bipolar disorder and heroine (and other opiate) addictions.
NMDA itself is an analogue of aspartate (can also act as a weak agonist at most glutamate receptors).
Blocking NMDA increases the activity of another receptor, AMPA, and that this boost in AMPA is crucial for ketamine’s rapid antidepressant actions. The study, through the National Institute of Health, was reported online in Biological Psychiatry on July 23, by NIMH researchers Husseini K. Manji, MD, Guang Chen, MD, PhD, et al.
So far, I have treated 18 patients with one treatment failure.