AMPA antagonists: do they hold more promise for clinical stroke trials than NMDA antagonists?

The cytoprotective effects of MK-801 and NBQX, selective N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists, respectively, were compared both singularly and in combination in models of transient severe forebrain and transient focal c...

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Auteurs principaux: Buchan, A, Lesiuk, H, Barnes, K, Li, H, Huang, Z, Smith, K, Xue, D
Format: Journal article
Langue:English
Publié: 1993
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author Buchan, A
Lesiuk, H
Barnes, K
Li, H
Huang, Z
Smith, K
Xue, D
author_facet Buchan, A
Lesiuk, H
Barnes, K
Li, H
Huang, Z
Smith, K
Xue, D
author_sort Buchan, A
collection OXFORD
description The cytoprotective effects of MK-801 and NBQX, selective N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists, respectively, were compared both singularly and in combination in models of transient severe forebrain and transient focal cerebral ischemia. After 10 minutes of four-vessel occlusion ischemia, the sodium salt of NBQX (30 mg/kg IP) given at the time of reperfusion and, subsequently, 15 and 30 minutes later produced a dramatic reduction in CA1 hippocampal necrosis at 7 days. This effect was not obtained with the intraperitoneal administration of either MK-801 (1 mg/kg x 3) or the combination of both NBQX and MK-801 given at the same time intervals. This effect of intraperitoneal NBQX alone was reproduced in a two-vessel occlusion/hypotension model using this same drug administration. Delayed treatment with both NBQX and GYKI 52466, but neither MK-801 nor the combination of NBQX and MK-801 given after a delay, produced a significant reduction in the mean volume of neocortical infarction after transient focal ischemia. We conclude that the AMPA receptor may play a more important role than the NMDA receptor in both selective ischemic necrosis of hippocampal neurons and in neocortical infarction. AMPA antagonists should be subjected to clinical stroke trials.
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spelling oxford-uuid:9741943e-d589-4df6-96e5-3a2bc3be60302022-03-26T23:58:16ZAMPA antagonists: do they hold more promise for clinical stroke trials than NMDA antagonists?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9741943e-d589-4df6-96e5-3a2bc3be6030EnglishSymplectic Elements at Oxford1993Buchan, ALesiuk, HBarnes, KLi, HHuang, ZSmith, KXue, DThe cytoprotective effects of MK-801 and NBQX, selective N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists, respectively, were compared both singularly and in combination in models of transient severe forebrain and transient focal cerebral ischemia. After 10 minutes of four-vessel occlusion ischemia, the sodium salt of NBQX (30 mg/kg IP) given at the time of reperfusion and, subsequently, 15 and 30 minutes later produced a dramatic reduction in CA1 hippocampal necrosis at 7 days. This effect was not obtained with the intraperitoneal administration of either MK-801 (1 mg/kg x 3) or the combination of both NBQX and MK-801 given at the same time intervals. This effect of intraperitoneal NBQX alone was reproduced in a two-vessel occlusion/hypotension model using this same drug administration. Delayed treatment with both NBQX and GYKI 52466, but neither MK-801 nor the combination of NBQX and MK-801 given after a delay, produced a significant reduction in the mean volume of neocortical infarction after transient focal ischemia. We conclude that the AMPA receptor may play a more important role than the NMDA receptor in both selective ischemic necrosis of hippocampal neurons and in neocortical infarction. AMPA antagonists should be subjected to clinical stroke trials.
spellingShingle Buchan, A
Lesiuk, H
Barnes, K
Li, H
Huang, Z
Smith, K
Xue, D
AMPA antagonists: do they hold more promise for clinical stroke trials than NMDA antagonists?
title AMPA antagonists: do they hold more promise for clinical stroke trials than NMDA antagonists?
title_full AMPA antagonists: do they hold more promise for clinical stroke trials than NMDA antagonists?
title_fullStr AMPA antagonists: do they hold more promise for clinical stroke trials than NMDA antagonists?
title_full_unstemmed AMPA antagonists: do they hold more promise for clinical stroke trials than NMDA antagonists?
title_short AMPA antagonists: do they hold more promise for clinical stroke trials than NMDA antagonists?
title_sort ampa antagonists do they hold more promise for clinical stroke trials than nmda antagonists
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