title: Pretreatment with the NMDA antagonist dextrorphan reduces cerebral injury following transient focal ischemia in rabbits.
abstract: We studied the efficacy of systemic pre-treatment with dextrorphan (DX), a clinically tested N-methyl-D-aspartate (NMDA) antagonist, in a rabbit model of transient focal cerebral ischemia. Rabbits were treated with either a 24 mg/kg i.v. loading dose followed by 12 mg/kg/h i.v. infusion of 0.48% DX in normal saline (NS), or with an equivalent volume of NS alone. One and 1/2 h after starting the drug or NS, the rabbits underwent a 1 h occlusion of the left internal carotid and anterior cerebral arteries, followed by 4 h of reperfusion. The DX-treated rabbits had significantly less neocortical ischemic neuronal damage (7.4%) than the normal saline group (31.6%) and demonstrated a significant decrease in ischemic cortical edema. DX may prove useful in the treatment of clinical cerebrovascular disease.
authors.affiliation: Division of Neurosurgery, Stanford University Medical Center, CA 94305.
authors.forename: G K
authors.initials: GK
authors.lastname: Steinberg
authors.forename: J
authors.initials: J
authors.lastname: Saleh
authors.forename: R
authors.initials: R
authors.lastname: DeLaPaz
authors.forename: D
authors.initials: D
authors.lastname: Kunis
authors.forename: S R
authors.initials: SR
authors.lastname: Zarnegar
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000037:antagonists & inhibitors; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001929:Brain Edema / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D003917:Dextrorphan / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000473:pathology* / Q000517:prevention & control; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011817:Rabbits
chemical_list: D009019:Morphinans; D003917:Dextrorphan; D001224:Aspartic Acid; D016202:N-Methylaspartate