N-methyl-D-aspartate (NMDA) receptors are glutamate gated ion channel receptors that play critical roles in synaptic transmission, synaptic plasticity, learning, and memory. NMDA receptors are also involved in various pathological conditions such as epilepsy, schizophrenia, neuropathic pain, and neurodegenerative disorders. Due to their role in these diseases, a variety of NMDA receptor-based therapeutics have been developed and tested in both pre-clinical and clinical studies. However, the majority of these drugs have had very disappointing results due to adverse side effects and limited efficacy. To overcome this problem researchers at the University of Nebraska Medical Center and the University of Bristol have created a library of subtype selective NMDA receptor compounds that have a novel allosteric modulator mechanism of action. This library consists of both NMDA receptor antagonists and NMDA receptor potentiators. Antagonists could be useful for blocking epilepsy, neuropathic pain and preventing death of neurons in neurodegenerative diseases while the potentiators could have use in cognitive enhancement and the treatment of schizophrenia, post-traumatic stress syndrome, and drug addiction.
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