Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system,
and diseases that associate a deficiency in GABA might benefit from GABAergic drugs.
Cerebellar Purkinje cells employ GABA as a neurotransmitter. Cortical cerebellar atrophy (CCA) shows Purkinje
cell loss, and ataxia caused by it was alleviated by gabapentin and pregabalin. Thus, CCA is proposed as a model
of selective deficiency in GABA in the cerebellum, which benefits clinically from administration of GABAergic
drugs, in a manner similar in which levodopa improves motor manifestations in Parkinson’s disease. Other ataxias
also benefited clinically from GABAergic drugs, as adult-onset GM2 gangliosidosis, olivopontocerebellar atrophy,
cerebellar ataxia with hypogonadism, spinocerebellar ataxias 1, 2 and 6, and adult-onset ataxia-telangiectasia. Complex neurochemical
diseases, as multiple-system atrophy, had ataxia worsened by GABAergic drugs. Various disorders with a deficiency in GABA content
had their manifestations relieved by admistration of GABAergic drugs, as one patient with progressive encephalomyelitis with rigidity,
whose muscular spasms were suppressed by a combination of gabapentin and tiagabine, and another with diaphragmatic myoclonus, who
required gabapentin and tiagabine for symptomatic control. On the contrary, GABAergic drugs were not effective in cervical dystonia,
amyotrophic lateral sclerosis, Parkinson’s disease and progressive supranuclear palsy, presumably because a deficiency in GABA is not
an essential neurochemical abnormality in these diseases. Research aimed at identifying effective therapies to treat cerebellar ataxias and
other motor disorders of the central nervous system is warranted. Meanwhile, therapeutic tests with GABAergic drugs might yield clinical
improvement in these diseases.