Huntington'S disease: Treatment with muscimol, A GABA‐mimetic drug

Abstract

Muscimol, a γ‐aminobutyric acid (GABA) analogue that exerts potent and specific agonist effects on GABA receptors, was administered orally to 10 patients with Huntington's disease. In this double‐blind study, muscimol treatment did not result in improvement in these patients' motor or cognitive functions. However, muscimol adminsitration did ameliorate chorea in the most severely hyperkinetic patient, and it was associated with the appearance of dystonic features, electroencephalographic changes, and behavioral alterations in some patients. These latter observations support a functional relationship between GABA‐ergic activity and the genesis of both dystonia and EEG abnormalities in humans. The therapeutic failure of muscimol indicates that the GABA disturbance in Huntington's disease does not alone account for the clinical features of this disorder. This investigation was funded by a grant from the Hereditary Disease Foundation, Beverly Hills, CA. The University of Rochester Clinical Research Center is supported by U.S. Public Health Service Research Grant RR‐00044 from the Division of Research Facilities and Resources, National Institutes of Health. Muscimol was provided by Smith, Kline, & French Laboratories and formulated by the Strong Memorial Hospital Pharmacy.