Epilepsy is a chronic neurological disorder marked by recurrent, unprovoked seizures arising from aberrant hypersynchronous neuronal firing within cortical and subcortical networks. A central framework explaining seizure generation is the excitatory–inhibitory imbalance hypothesis, wherein reduced γ-aminobutyric acid (GABA)–mediated inhibition and excessive glutamate-driven excitation disrupt neuronal homeostasis (Treiman, 2001; Meldrum, 2002). GABA acts as the principal inhibitory neurotransmitter through GABAAA and GABABB receptor systems, while glutamate is the primary excitatory neurotransmitter acting via NMDA, AMPA, and kainate receptors (Scharfman, 2007). Modern antiepileptic drugs (AEDs) strategically target these pathways: GABAergic therapies enhance inhibitory tone through receptor potentiation, reuptake inhibition, or increased synaptic GABA availability, whereas glutamatergic modulators suppress pathologic excitation by antagonizing NMDA/AMPA receptors or reducing presynaptic glutamate release (Macdonald Baulac & Pitkänen, 2020). Collectively, understanding the differential and complementary roles of ABAergic and glutamatergic modulation provides a foundation for precision-based antiepileptic therapy and the development of next-generation interventions.
Vaibhav* et al. (Sat,) studied this question.