Eliprodil (codenamed SL-82.0715) is an

NMDA antagonist NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor ( NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce ...

drug candidate which selectively inhibits the NR2B (GLUN2B) subtype NMDA receptor at submicromolar concentrations. Eliprodil failed a Phase III clinical trial for the treatment of acute

ischemic stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop funct ...

in 1996, sponsored by Synthélabo Recherche.The Pharma Letter. 2 December 199
Synthelabo's Eliprodil Fails In Stroke Trials
/ref> NMDA receptors are a key component in mediating glutamate-induced

excitotoxicity In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate ...

, and it is believed that

NMDA antagonists NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor ( NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induc ...

would be

neuroprotective Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal los ...

after a stroke or other

traumatic brain injury A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic br ...

. After a traumatic brain injury, neurons become deprived of glucose and oxygen. These neurons quickly lose ATP and become depolarized, which releases glutamate. The extracellular buildup of glutamate triggers the overstimulation of

AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate. There are several types of glutamatergic ...

and NMDA receptors. This, in turn, causes an influx of Na⁺ and Ca²⁺. Therefore, when NMDA receptors are activated, there is an increase in intracellular Ca²⁺ concentration. High Ca²⁺ causes fatal metabolic consequences, including neuronal cell death.

References

Abandoned drugs Chloroarenes NMDA receptor antagonists Fluoroarenes Phenylethanolamines Piperidines {{nervous-system-drug-stub