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...
Auteurs principaux: | , , , , , , |
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Format: | Journal article |
Langue: | English |
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1993
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_version_ | 1826286334328700928 |
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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. |
first_indexed | 2024-03-07T01:42:13Z |
format | Journal article |
id | oxford-uuid:9741943e-d589-4df6-96e5-3a2bc3be6030 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T01:42:13Z |
publishDate | 1993 |
record_format | dspace |
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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