title: Protection against ischaemic neuronal damage by drugs acting on excitatory neurotransmission.
abstract: An excitotoxic action of glutamate and aspartate contributes to the pathological outcome after transient global cerebral ischaemia, focal ischaemia, neonatal hypoxia/ischaemia, and secondary ischaemia following brain trauma. This provides a therapeutic approach utilising drugs acting on (i) glutamate release, (ii) postsynaptic glutamate receptors, and (iii) the secondary events following receptor activation (including the arachidonic acid cascade). Both NMDA and non-NMDA receptors are involved in the excitotoxic effects of glutamate and aspartate. The availability of competitive and noncompetitive antagonists acting at the NMDA receptor has permitted the demonstration of cerebroprotective effects of these compounds in animal models of global, focal, neonatal, and secondary cerebral ischaemia. Protection is seen with antagonist administration prior to and after the onset of ischaemia. The postischaemic therapeutic time window is not fully defined for the different models but is in the range of 0-20 min for incomplete global ischaemia and 1-3 h for focal ischaemia. The clinical usefulness of this approach remains to be established.
authors.affiliation: Department of Neurology, Institute of Psychiatry, London, United Kingdom.
authors.forename: B
authors.initials: B
authors.lastname: Meldrum
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D009422:Nervous System Diseases / Q000209:etiology* / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate