Open-channel blockers of the NMDA receptor complex.
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 alpha-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.
Albensi
Benedict C
BC
Department of Pharmacology and Therapeutics, School of Medicine, University of Manitoba, Division of Neurodegenerative Disorders, St. Boniface General Hospital Research Centre, 351 Taché Ave., Winnipeg, Manitoba, Canada. balbensi@sbrc.ca
Ilkanich
Erin
E
D000818:Animals; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000627:therapeutic use*; D013111:Spider Venoms / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
D007473:Ion Channels; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D013111:Spider Venoms