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

Journal article

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.

Authors: Buchan, A; Lesiuk, H; Barnes, K; Li, H; Huang, Z

• Publication status: Published
• Journal: Stroke; a journal of cerebral circulation
• Volume: 24
• Issue: 12 Suppl
• Pages: I148-I152
• Publication date: 1993-12-01
• EISSN: 1524-4628
• ISSN: 0039-2499
• Language: English
• Keywords: Drug Administration Schedule; Cerebrovascular Disorders; Quinoxalines; Anti-Anxiety Agents; Animals; Rats, Wistar; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Rats; Male; Injections, Intraperitoneal; Benzodiazepines; Cerebral Infarction; Dizocilpine Maleate; Reperfusion; N-Methylaspartate