Enhancing GABA inhibition is the next generation of medications for essential tremor.

Abstract

γ-Aminobutyric acid (GABA) is the most prevalent inhibitory CNS neurotransmitter. Activating GABA-A receptors hyperpolarizes cells via Cl^- influx, which inhibits action potentials. Although the exact pathophysiologies of tremor are incompletely understood, proposed neuroanatomy extensively implicates GABA pathways. Pathological studies and imaging studies also show GABA abnormalities in patients with ET. Most importantly, medications that activate GABA-A receptors, such as primidone, often improve tremor. Ongoing clinical trials and physiology research should further refine potential future GABAergic targets and treatments, which are currently the most promising targets for pharmacological intervention.