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Competitive Gly/NMDA receptor antagonists.

Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) where it is involved in the physiological regulation of different processes. It has been well established that excessive endogenous Glu is associated with many acute and chronic neurodegenerative disorders such as cerebral ischemia, epilepsy, amiotrophic lateral sclerosis (ALS), Parkinson's and Alzheimer's diseases. In addition to the classical competitive glutamate receptor (GluR) antagonists, much effort has been directed toward the development of many different non-competitive antagonists of these receptors and, among them, compounds blocking the glycine site on the NMDA receptor complex (Gly/NMDA) have been widely investigated. Many Gly/NMDA receptor antagonists showed to be potential therapeutic agents in many neurological diseases such as stroke, epilepsy and neuropathic pain. Some of them, endowed also with favourable physicochemical properties and low secondary undesiderable effects, reached clinical trials.

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