In addition, NMDA receptors get overstimulated by an increase in the neurotransmitter glutamate-enough to kill cells.
In brain tissue affected by stroke or traumatic injury, the environment becomes more acidic because of the lack of oxygen and the buildup of metabolites such as lactic acid. NMDA receptors are abundant on the surfaces of brain cells and play key roles in healthy processes such as memory formation. The drugs phencyclidine (also known as PCP) and ketamine are NMDA receptor antagonists their ability to block all subtypes of NMDA receptors is thought to account for their psychoactive side effects. At the same time, giving mice 93-31 does not seem to lead to the side effects seen with other NMDA receptor antagonists. In a mouse model of ischemic stroke, a NMDA receptor antagonist called 93-31 can reduce the volume of damaged brain tissue by more than half, researchers found. This is a proof of concept study that shows this mechanism of action could potentially be exploited clinically in several conditions, such as stroke, traumatic brain injury and subarachnoid hemorrhage." "These compounds are most active when the pH is lowered by biochemical processes associated with injury of the surrounding tissue. "We have found neuroprotective compounds that can limit damage to the brain during ischemia associated with stroke and other brain injuries, but have minimal side effects," says senior author Stephen Traynelis, PhD, professor of pharmacology at Emory University School of Medicine. Now researchers have found a potential path around this obstacle.