GABAergic Pharmacotherapy in the Treatment of Motor Disorders of the Central Nervous System

Author(s): Jose Gazulla, Carlota Ruiz-Gazulla, Maria Tintore.

Journal Name: Current Pharmaceutical Design

Volume 21 , Issue 34 , 2015

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Abstract:

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.

Keywords: GABAergic drugs, cortical cerebellar atrophy, olivopontocerebellar atrophy, autosomal dominant spinocerebellar ataxia, multiple- system atrophy, cerebellar ataxia with hypogonadism, progressive encephalomyelitis with rigidity, diaphragmatic myoclonus.

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Article Details

VOLUME: 21
ISSUE: 34
Year: 2015
Page: [4989 - 4995]
Pages: 7
DOI: 10.2174/1381612821666150914120923
Price: $58

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