title: NMDA/NR2B selective antagonists in the treatment of ischemic brain injury.
abstract: Glutamate is the main excitatory neurotransmitter in the central nervous system and it plays a significant role not only in synaptic transmission but also in acute and chronic neuropathologies including stroke. Presently, four receptors for glutamate have been identified and the NMDA receptor family is the most intensively studied. A number of NMDA receptor antagonists have been developed and used for treatment of neurological diseases in patients. However, all of these drugs have been failed in clinical trials either because of intolerable side effects or lack of medical efficacy. Recently, the understanding of molecular structure of NMDA receptors has been advanced and this finding thus provides information for designing subtype-selective antagonists. Using NR2B subunit selective antagonists, ifenprodil and eliprodil, as basic structure models, second and third generation congeners have been developed. Several NR2B-selective compounds showed neuroprotective actions at doses that did not produce measurable side effects in preclinical studies. Some of NR2B subunit selective antagonists have also been tested for the treatment of ischemic brain injury. The present review describes the role of glutamate in ischemic brain injury with an emphasis on the NR2B containing NMDA receptors.
authors.affiliation: Stroke Research Laboratory, Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: Chen Xu
authors.initials: CX
authors.lastname: Wang
authors.forename: Ashfaq
authors.initials: A
authors.lastname: Shuaib
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy*; D020916:Conotoxins / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000078328:Felbamate; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D048448:Phenylcarbamates; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011409:Propylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D011487:Protein Conformation; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D020916:Conotoxins; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D010880:Piperidines; D011409:Propylene Glycols; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C055407:conotoxin GV; C095106:traxoprodil mesylate; C010739:ifenprodil; D000078328:Felbamate; C058083:eliprodil