Zonisamide inhibits nitric oxide synthase activity induced by N-methyl-D-aspartate and buthionine sulfoximine in the rat hippocampus. 1999

Y Noda, and A Mori, and L Packer
Department of Molecular and Cell Biology, University of California at Berkeley, 94720-3200, USA.

The antiepileptic zonisamide (ZNS) is known to be effective in protecting against epilepsy in a wide variety of animal epilepsy models and in humans with epileptic seizures, with both partial and generalized seizures. ZNS scavenges hydroxyl radicals (OH*) and nitric oxide (NO) in a dose-dependent manner. The mechanism of the antiepileptic effect of ZNS may involve protection of neurons from free radical damage and stabilization of neuronal membranes. In this study, the effect of ZNS on nitric oxide synthase (NOS) activity in the hippocampus of rats induced by N-methyl-D-aspartate (NMDA) with/without L-buthionine-[S, R]-sulfoximine (BSO) was examined. NOS activity was accelerated significantly (plus 93%) in the hippocampus 3 hours after NMDA injection (30 mg/Kg, i.p.), and (plus 220%) 3 hours after NMDA (30 mg/Kg, i.p.) injection into BSO-pretreated rats (150 mg/Kg, i.p.). NOS activity was not affected by ZNS itself. ZNS reduced NOS activity, accelerated by NMDA- with/without BSO-treatment, to the control level in the hippocampus. This suggests that ZNS may inhibit initiation and propagation of seizures by inhibiting NOS activity, and also may protect neurons from free radical damage by NO and/or OH*.

UI MeSH Term Description Entries
D007555 Isoxazoles Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions. Isoxazole
D004790 Enzyme Induction An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Induction, Enzyme
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000078305 Zonisamide A benzisoxazole and sulfonamide derivative that acts as a CALCIUM CHANNEL blocker. It is used primarily as an adjunctive antiepileptic agent for the treatment of PARTIAL SEIZURES, with or without secondary generalization. 3-Sulfamoylmethyl-1,2-benzisoxazole,AD 810,AD-810,CI 912,CI-912,Zonegran,Zonisamide Monosodium,3 Sulfamoylmethyl 1,2 benzisoxazole,AD810,CI912
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000927 Anticonvulsants Drugs used to prevent SEIZURES or reduce their severity. Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic
D016202 N-Methylaspartate An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA). N-Methyl-D-aspartate,NMDA,N-Methyl-D-aspartic Acid,Acid, N-Methyl-D-aspartic,N Methyl D aspartate,N Methyl D aspartic Acid,N Methylaspartate
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

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