Zonisamide inhibits nitric oxide synthase activity induced by N-methyl-D-aspartate and buthionine sulfoximine in the rat hippocampus.
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*.
Noda
Y
Y
Department of Molecular and Cell Biology, University of California at Berkeley, 94720-3200, USA.
Mori
A
A
Packer
L
L
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000078305:Zonisamide
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D000078305:Zonisamide; D019328:Buthionine Sulfoximine; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; D005978:Glutathione