Role of excitatory amino acid antagonists in the management of birth asphyxia.
Birth asphyxia is an important cause of permanent neuro-developmental disability. Asphyxia sets in course a progression of intracellular events which culminates in neuronal death, and this process may take up to 48 h to complete. Entry of calcium into the neurone appears to be the key to the cell death, and it is known that during asphyxia, excessive glutamate is released which stimulates the voltage-dependent N-methyl-D-aspartate (NMDA) receptor to open with an accumulation of excess intracellular calcium. MK-801 is a very effective NMDA receptor antagonist, and it has been shown that this drug prevents or significantly reduces the extent of cortical neurone infarction following experimental asphyxia in 7-day-old rat pups. Unfortunately, MK-801 is toxic to the pup, but newer NMDA receptor antagonists may offer the opportunity for neuroprotection in the human infant who has suffered severe birth asphyxia.
Malcolm Levene Academic Unit of Paediatrics and Child Health, Department of Clinical Medicine, University of Leeds, UK.
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D000596:Amino Acids / Q000037:antagonists & inhibitors*; D000818:Animals; D001238:Asphyxia Neonatorum / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology; D016291:Dizocilpine Maleate / Q000009:adverse effects / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006801:Humans; D007231:Infant, Newborn; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013569:Synapses / Q000378:metabolism
D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate