Effects of NMDA and calcium channel antagonists on regional cerebral blood flow.
N-Methyl-D-aspartate (NMDA) antagonists and voltage-dependent calcium channel antagonists were tested to determine potential effects on regional cerebral blood flow in the normal rabbit brain. Ketamine had no effects on cortical or hippocampal blood flow, but was found to significantly decrease blood flow in the inferior colliculus. MK-801 decreased blood flow in almost all regions of the brain tested. On the other hand, nimodipine significantly increased flow in the cortex, hippocampus, and tegmentum. Dextromethorphan and dextrorphan, which have been shown to act at the NMDA receptor as well as the dihydropyridine calcium channel, decreased blood flow in the inferior colliculus, but showed no effects in the cortex or hippocampus. These results suggest that the neuroprotective NMDA antagonists do not increase blood flow primarily in the normal brain.
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Department of Neurosurgery, Stanford University School of Medicine, CA 94305.
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Steinberg
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003915:Dextromethorphan / Q000494:pharmacology; D003917:Dextrorphan / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology; D008636:Mesencephalon / Q000098:blood supply; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009553:Nimodipine / Q000494:pharmacology; D011817:Rabbits; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D012249:Rhombencephalon / Q000098:blood supply
D002121:Calcium Channel Blockers; D003917:Dextrorphan; D009553:Nimodipine; D016202:N-Methylaspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D003915:Dextromethorphan