The GABAergic system in motion sickness: a narrative review from the vestibular molecular brake to clinical evidence

Resumo

Background: Motion sickness is a prevalent and temporarily incapacitating condition, traditionally managed with anticholinergics and antihistamines that act downstream in the emetic cascade. The GABAergic system — the main inhibitory pathway of the central nervous system — has received growing attention as a rational therapeutic target but remains underrepresented in reviews of the field.

Objective: To critically review the neurophysiological and pharmacological basis underlying the role of gamma-aminobutyric acid (GABA) in the pathophysiology and treatment of motion sickness.

Methods: Narrative review of the literature, synthesizing evidence from vestibular neurophysiology, clinical pharmacology, and controlled trials.

Results: The brainstem velocity storage mechanism, indexed by the time constant of the angular vestibulo-ocular reflex (TVOR), correlates directly with motion sickness susceptibility and is modulated by GABA-B receptors on vestibular-only neurons. Agents that enhance GABAergic tone — from baclofen, as mechanistic proof of concept, to benzodiazepines — raise the motion sickness threshold. Recent randomized clinical evidence demonstrated that a combination of GABA and neuroactive cofactors was superior to ginger extract in the management of chronic complaints consistent with motion sickness.

Conclusion: The GABAergic system is a mechanistically grounded and clinically promising therapeutic target for motion sickness, supporting the development of next-generation modulators and combination strategies.