Alterations of nitric oxide and monoamines in the brain of the EL mouse treated with phenobarbital and zonisamide.
The effects of phenobarbital (PB; doses, 5, 10, and 25 mg/kg, intraperitoneally (i.p.)) and zonisamide (ZNS; doses, 30, 75, and 150 mg/kg, i.p.) on nitric oxide (NO) production, and those of coadministration of PB (5 mg/kg, i.p.) and ZNS (75 mg/kg, i.p.) on monoamines in the brain of the seizure-susceptible EL mouse were investigated. Nitric oxide production was obtained by measuring the combined level of nitrite plus nitrate (NOx). Zonisamide and PB dose-dependently suppressed the seizure of the EL mouse, and coadministration of PB (5 mg/kg) and ZNS (75 mg/kg) induced a greater degree of seizure suppression than treatment with ZNS or PB alone. Although PB (5 mg/kg) had no effect on brain NOx levels, ZNS (150 mg/kg) and coadministration of ZNS (75 mg/kg) and PB (5 mg/kg) decreased NOx levels significantly. Phenobarbital (5 mg/kg) did not influence monoamines, while coadministration of PB (5 mg/kg) and ZNS (75 mg/kg) decreased dihydroxyphenylacetic acid and increased 5-HT concentrations. The effect of the coadministration of two drugs on monoamines were similar to that of ZNS alone. These results suggest that one of the anticonvulsant effects of coadministration of PB and ZNS may be caused by changes in NOx levels.
Tominaga
M
M
Department of Neuropsychiatry, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Nagatomo
I
I
Uchida
M
M
Hashiguchi
W
W
Akasaki
Y
Y
Takigawa
M
M
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008818:Mice, Neurologic Mutants; D009569:Nitric Oxide / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology* / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D000078305:Zonisamide
D000927:Anticonvulsants; D015306:Biogenic Monoamines; D007555:Isoxazoles; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D000078305:Zonisamide; D010634:Phenobarbital