A study by researchers indicates that Gabapentin binds to the α2-δ subunit of the voltage-dependent P/Q calcium channel and has been shown to stimulate expression of δGABAA receptors, to increase inhibitory tone in mouse cerebellum, and to increase brain γ-aminobutyric acid (GABA) concentration in healthy volunteers. Peak serum concentration (Tmax) of gabapentin occurs 2 to 3 hours after ingestion, its half-life (t1/2) being between 5 and 7 hours.
GABA is the most important inhibitory neurotransmitter in the central nervous system. In the cerebellum, it is used by Purkinje cells to provide inhibitory outflow to the cerebellar nuclei. GABA content in the dentate nuclei of the cerebellum and cerebrospinal fluid has been found to be markedly and selectively reduced in late cortical cerebellar atrophy.
In a previous study, 10 patients with cortical cerebellar atrophy were examined at baseline conditions and 3 hours after single doses of 400 mg of gabapentin. Intermalleolar distance (in centimeters) and the International Cooperative Ataxia Rating Scale items “walking capacities,” “spread of feet,” “knee-tibia test,” and “finger-to-nose test” were assessed: a clinical and statistically significant improvement was found in every item when comparing the scores recorded after three single-dose administrations of gabapentin with those at baseline; the clinical benefit weaned off after several hours. Thus, gabapentin’s switchlike effect on cerebellar ataxia was demonstrated.
Gabapentin should be considered as a viable therapeutic agent for cerebellar ataxias and other motor disorders caused by a lack of GABA activity in the central nervous system, based on its efficacy and tolerability, in which single doses of this medicine could predict long-term clinical improvement.
Reference link-movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28687
