title: Delayed treatment with dextromethorphan and dextrorphan reduces cerebral damage after transient focal ischemia.
abstract: The N-methyl-D-aspartate (NMDA) antagonists dextromethorphan (DM) and dextrorphan (DX) were found to reduce significantly neocortical severe ischemic neuronal damage (SIND) when administered in a delayed fashion after the ischemic insult. Rabbits underwent occlusion of the left internal carotid artery and anterior cerebral artery for 1 h, followed by 4 h of reperfusion. Immediately after the completion of the 1 h arterial occlusion, animals were blindly treated intravenously with 20 mg/kg loading dose followed by 10 mg/kg/h of DM, 15 mg/kg loading dose followed by 15 mg/kg/h of DX, or an equivalent volume of normal saline (NS) alone. The area of neocortical SIND was 3.7% in the DM group, 4.4% in the DX group, and 41.3% in the normal saline controls. These drugs may have considerable therapeutic potential in clinical stroke.
authors.affiliation: Division of Neurosurgery, Stanford University School of Medicine, CA 94305.
authors.forename: G K
authors.initials: GK
authors.lastname: Steinberg
authors.forename: J
authors.initials: J
authors.lastname: Saleh
authors.forename: D
authors.initials: D
authors.lastname: Kunis
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D002545:Brain Ischemia / Q000188:drug therapy*; D003915:Dextromethorphan / Q000494:pharmacology / Q000627:therapeutic use*; D003917:Dextrorphan / Q000494:pharmacology / Q000627:therapeutic use*; D007981:Levorphanol / Q000031:analogs & derivatives*; D008297:Male; D009019:Morphinans / Q000627:therapeutic use*; D016202:N-Methylaspartate; D011817:Rabbits
chemical_list: D009019:Morphinans; D003917:Dextrorphan; D007981:Levorphanol; D001224:Aspartic Acid; D016202:N-Methylaspartate; D003915:Dextromethorphan