Serum nitrite and nitrate levels were determined in 34 epileptic children treated with valproic acid and 23 with carbamazepine and compared to 38 non-active epileptic children with no antiepileptic drug therapy, in a study at KSU Medical School, Turkey. Nitrite and nitrate levels, metabolites of nitric oxide, were significantly higher in both valproic acid and carbamazepine-treated groups compared to controls (p<0.01), and nitrate but not nitrite was significantly higher in the valproic acid-treated group compared to the carbamazepine group (p<0.01). Serum drug levels did not correlate with nitrite and nitrate levels. The authors suggest that valproic acid and carbamazepine might exert an antiepileptic effect through nitric oxide. [1]

COMMENT. Nitrite and nitrate levels are used as indicators of nitric oxide (NO) levels in serum. NO has been found to have an anticonvulsant effect in animal studies. The above report suggests that the anticonvulsants, valproic acid and carbamazepine, may have antiepileptic effects through NO accumulation.

Valproic acid (VPA) blood gene expression patterns and epilepsy. The expression of 461 genes was altered in VPA-treated compared with drug-free children with epilepsy, in a study at the University of Cincinnati [2]. A new mechanism of action of VPA is suggested that involves down-regulation of serine threonine kinases and a separate genomic profile that correlates with VPA-induced seizure freedom.