title: Secobarbital attenuates excitotoxicity but potentiates oxygen-glucose deprivation neuronal injury in cortical cell culture.
abstract: We examined the effects of secobarbital and other sedative-hypnotic barbiturates on the neuronal death induced by exposure to excitatory amino acids or deprivation of oxygen or glucose in mouse cortical cell cultures. N-Methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate, and kainate toxicities were attenuated in a concentration-dependent fashion by high concentrations of secobarbital or thiopental. Antagonism of NMDA toxicity was not overcome by increasing NMDA concentration and not mimicked by gamma-aminobutyrate. Despite these antiexcitotoxic actions, secobarbital exacerbated the neuronal death induced by deprivation of either glucose alone or oxygen and glucose together; death induced by oxygen deprivation alone was little affected. Thiopental and methohexital also increased oxygen-glucose deprivation injury. A possible explanation for this injury potentiation was provided by the observation that secobarbital enhanced the cellular ATP depletion induced by combined oxygen-glucose deprivation. Deleterious effects on ATP production may counterbalance the protective effects of barbiturates under some conditions.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, CA 94305-5123.
authors.forename: R G
authors.initials: RG
authors.lastname: Giffard
authors.forename: J H
authors.initials: JH
authors.lastname: Weiss
authors.forename: R A
authors.initials: RA
authors.lastname: Swanson
authors.forename: D W
authors.initials: DW
authors.lastname: Choi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology*; D005947:Glucose / Q000172:deficiency*; D000860:Hypoxia / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D012631:Secobarbital / Q000494:pharmacology*
chemical_list: D009498:Neurotoxins; D012631:Secobarbital; D000255:Adenosine Triphosphate; D005947:Glucose