Midafotel (CPPene; SDZ EAA 494) is a potent,

competitive Competition is a rivalry where two or more parties strive for a common goal which cannot be shared: where one's gain is the other's loss (an example of which is a zero-sum game). Competition can arise between entities such as organisms, indivi ...

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...

at the

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and ...

. It was originally designed as a potential therapy for

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 ...

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...

neuropathic pain Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...

. It looked very promising in ''in vitro'' trials proving to be a potent competitive antagonist at the NMDA without affecting other receptors. Research continued through to ''in vivo'' cat studies where it proved to limit damage after occluding the middle cerebral artery, leading to ischaemia. It also blocked photosensitive epilepsies in baboons. CPPene had a pharmacokinetic profile suitable for progressing to clinical trials, as it has no toxic byproducts, is excreted exclusively via the renal system, and remains unchanged in the brain. However, CPPene was removed from clinical trials, as it provided no suitable neuronal protection or beneficial treatment for epilepsy, and had side effects which led to many patients withdrawing from trials. A possible explanation for its lack of efficacy in trials is the relatively short therapeutic time window following ischaemic damage and the fact that a small amount of glutamate helps neuronal survival. It is also believed that some "pro-survival" genes are activated by NMDA receptors.

References

{{Ionotropic glutamate receptor modulators Carboxylic acids NMDA receptor antagonists Phosphonic acids Piperazines

See also

References