Alterations of nitric oxide and monoamines in the brain of the EL mouse treated with phenobarbital and zonisamide

Abstract

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 dosedependently 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.

Inhibition of hyperactivity and impulsivity by carbonic anhydrase inhibitors in spontaneously hypertensive rats, an animal model of ADHD

“…Therefore, CA inhibitors can increase dopamine release in ventral tegmental area, which involves in the delayed reward system and the pathogenesis of ADHD (Dichter et al 2012;Sonuga-Barke 2005). In addition, zonisamide, an antiepileptic drug with CA inhibitory activity, has been reported to increase extracellular and intracellular dopamine concentration in rodents (Okada et al 1995;Tominaga et al 2001). Furthermore, zonisamide is used to treat impulsivity control disorder in Parkinson's disease (Bermejo et al 2010).…”

“…Acetazolamide (AZ), an inhibitor of CA, has been used as an anticonvulsant since 1952 (Bergstom et al 1952), and the anticonvulsant activity of CA inhibitors, including AZ and methazolamide (MZ), has been reported to involve noradrenergic mechanisms (Gray and Rauh 1974;Torchiana et al 1973). Zonisamide, another CA inhibitor and anticonvulsant, stimulates Ca 2+ -evoked monoamine release (Kawata et al 1999;Tominaga et al 2001) and has been shown to be beneficial for patients with Parkinson's disease (Bermejo et al 2010;Murata 2010). In addition, CA has been shown to affect the switching of gamma-aminobutyric acid (GABA) A receptors between excitation and inhibition (Ting et al 2013).…”

Plasma nitrate and nitrite levels of patients with eating disorders

“…2 Nitric oxide has been studied in relation to the etiologies of various nervous and mental diseases, including schizophrenia, anxiety, depression 3 and epilepsy. 4 However, little is known about the relationship of NO and eating disorders (ED).…”

Zonisamide

“…In mice models, ZNS was shown to decrease nitric oxide levels in a dose-dependent fashion. 9 Nitric oxide modulates many brain functions and is involved in the pathogenesis of convulsive seizures by promoting neuronal synchronization. Although ZNS has a sulfamoyl side chain group (similar to acetazolamide), it does not seem to exert significant carbonic anhydrase activity, so this is an unlikely contributor to its antiseizure actions.…”