NMDA antagonists epilepsy

Substituted y-lactone derivatives, (HI), prepared by Sundermann (3) were effective as NMDA antagonists and used in treating chronic pain, neuropathic pain, and epilepsy. 

Keywords Ionotropic receptors Co-agonism NMDA antagonists Glycine antagonists Stroke Pain Metabotropic receptors Epilepsy... 

Epilepsy NMDA antagonists mGlu, antagonists mGlu2/i agonists... 

The action of glutamate in epilepsy is assumed to be the consequence of NMDA-receptor binding and of AMPA-receptor activation as well. In vivo kindling studies provoke epileptic activity. In vitro application of glutamate on hippocampal cell cultures burst firing. These phenomena can be reduced by NMDA antagonists. 

Perin-Dureau F, RachUne J, Neyton J, Paoletti P (2002) Mapping the binding site of the neuroprotectant ifenprodU on NMDA receptors. J Neurosd 22 5955-5965 Rogawski MA (1992) The NMDA receptor, NMDA antagonists and epilepsy therapy. A status report. Drugs 44 279-292... 

On the basis of the events that occur in pain and LTP, it is easy to see how the actions of glutamate relate to the excessive firing of neurons — as yet no NMDA receptor antagonist has been tested in human epilepsy. 

Although epilepsy was one of the first suggested therapeutic appUcations of NMDA receptor antagonists (Czuczwar and Meldrum 1982 Meldrum 1985)... 

Fig. 10.2 Chemical structures of NMDA and AMPA antagonists used for the treatment of ischemic injury, epilepsy and head injury in human subjects. Eliprodil (a) ifenprodil (b) remacemide (c) selfotel (d) and aptiganel (e)...

Yen W., Williamson J., Bertram E. H., and Kapur J. (2004). A comparison of three NMDA receptor antagonists in the treatment of prolonged status epilepticus. Epilepsy Res. 59 43-50. 

Several NMDA receptor antagonists have been synthesized and tested in stroke models, epilepsy models, and in clinical trials. Many of the antagonists are limited by side effects such as hemodynamic abnormalities, hypotension, neuronal vacuolation, memory disturbances, cognitive disturbances, motor dysfunction, seizures, hallucinations, unpleasant dreams, psychotomimetic episodes, and other effects. This has made the search difficult for NMDA receptor antagonists that can be used as neu-roprotective agents. 

---