TY - JOUR
T1 - Open-channel blockers of the NMDA receptor complex
AU - Albensi, Benedict C.
AU - Ilkanich, Erin
AU - Mattson, Mark
AU - Liang, Jennifer
PY - 2004/11
Y1 - 2004/11
N2 - A variety of compounds have been shown to limit or prevent excitotoxicity by blocking N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. However, many first-generation NMDA antagonists did not live up to clinical expectations in trials of acute brain injury because of the manifestation of multiple side effects. In spite of this, development of NMDA antagonists continues, where some of the newer agents block excitotoxicity through alternative mechanisms. For example, blockers selective to the NR2B subunit or agents that block metabotropic glutamate receptors or α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid receptors are currently under investigation. Several years ago, the arylalkylamine spider toxins were demonstrated to function as open-channel blockers similar to memantine, which was very recently approved by the U.S. FDA for use in patients with Alzheimer's dementia. With this said, programs focusing on NMDA antagonism via alternative mechanisms may still hold promise for treating acute injury and even chronic forms of dementia.
AB - A variety of compounds have been shown to limit or prevent excitotoxicity by blocking N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. However, many first-generation NMDA antagonists did not live up to clinical expectations in trials of acute brain injury because of the manifestation of multiple side effects. In spite of this, development of NMDA antagonists continues, where some of the newer agents block excitotoxicity through alternative mechanisms. For example, blockers selective to the NR2B subunit or agents that block metabotropic glutamate receptors or α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid receptors are currently under investigation. Several years ago, the arylalkylamine spider toxins were demonstrated to function as open-channel blockers similar to memantine, which was very recently approved by the U.S. FDA for use in patients with Alzheimer's dementia. With this said, programs focusing on NMDA antagonism via alternative mechanisms may still hold promise for treating acute injury and even chronic forms of dementia.
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U2 - 10.1358/dnp.2004.17.9.872569
DO - 10.1358/dnp.2004.17.9.872569
M3 - Article
C2 - 15645013
AN - SCOPUS:12344265011
SN - 0214-0934
VL - 17
SP - 557
EP - 562
JO - Drug News and Perspectives
JF - Drug News and Perspectives
IS - 9
ER -