GABA Modulators in Epilepsy

Introduction

• A seizure is a transient alteration of behaviour from disordered, synchronous, high-frequency firing of cortical neuron populations; a seizure can be triggered by either a reduction of inhibitory (GABAergic) activity or an enhancement of excitatory (glutamatergic) activity.
• GABA as a target — GABA is the major inhibitory transmitter; enhancing GABA-mediated inhibition increases Cl^- influx → membrane hyperpolarization → raised seizure threshold and reduced high-frequency firing.
• Pharmacological proof: GABA_A antagonists (bicuculline, picrotoxin) provoke seizures, whereas agents that enhance GABA-mediated inhibition suppress them across diverse models.
• Scope — GABA modulators in epilepsy are the GABAergic arm of antiseizure therapy — GABA_A allosteric modulators (benzodiazepines, barbiturates, clobazam), the GABA-transaminase inhibitor vigabatrin, the GABA-reuptake inhibitor tiagabine, and the GABA-analogue adjuncts gabapentin/pregabalin (whose true target is the α₂δ-1 Ca²⁺-channel subunit, not GABA).