Anticonvulsant role of nitric oxide synthase inhibitors in epilepsy (Review).

Epilepsy is a pathophysiological process triggered by an imbalance between excitatory and inhibitory mechanisms in the brain, resulting in the sudden and synchronized excessive electrical discharges of neurons. Nitric oxide (NO) is a cellular signaling molecule that functions as both a neurotransmitter and neuromodulator in the central nervous system. Despite its critical role in neuronal function, the impact of the NO pathway on the pathophysiology of epilepsy remains complex. NO, produced by different isoforms of the NO synthase (NOS) enzyme, exerts a bidirectional effect on epileptogenesis. In the present review, the effects of non-selective NOS inhibitors (L-NAME) and isoform-specific selective neuronal NOS (nNOS; 7-nitroindazole) and inducible NOS (iNOS; aminoguanidine) inhibitors on seizure threshold, seizure duration and neuroinflammation are comparatively discussed. Evidence indicates that the selective inhibition of nNOS and iNOS activity significantly suppresses glutamatergic hyperexcitability and nitrosative stress associated with N-methyl-D-aspartate receptor activation. nNOS inhibition increases neuronal survival and reduces seizure severity by decreasing intracellular Ca