title: THIP treatment of Huntington's disease.
abstract: We evaluated the therapeutic efficacy of gamma aminobutyric acid (GABA) system stimulation in four patients with classical Huntington's disease and one with the hypokinetic-rigid form. Orally administered THIP (4,5,6,7-tetrahydroisoxazolo-[5,4,-c] pyridin-3-ol), a novel GABA receptor agonist, failed to improve motor or cognitive function during a 2-week trial. At maximum levels, THIP mimicked another putative GABA agonist, muscimol, in causing unsteadiness of gait, diminished attention to sensory stimuli, and somnolence. These effects suggest that central GABA systems participate in the regulation of some human and behavioral functions. CSF content of homovanillic acid, a major metabolite of dopamine, increased during high-dose THIP therapy, suggesting that augmentation of dopaminergic function may have contributed to the drug's lack of efficacy.
mesh_terms: D000328:Adult; D002986:Clinical Trials as Topic; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006816:Huntington Disease / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D007555:Isoxazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010080:Oxazoles / Q000627:therapeutic use*
chemical_list: D007555:Isoxazoles; D010080:Oxazoles; C015542:gaboxadol; D006719:Homovanillic Acid