Glutamatergic therapy of Huntington's chorea.
Preclinical evidence suggests that hypofunction of the glutamatergic subthalamopallidal tract may contribute to the hyperkinesis in Huntington's chorea. The clinical effects of milacemide, a glycine prodrug, were studied in seven patients with Huntington's disease under double-blind, placebo-controlled conditions. Oral doses of 1,200 mg/day did not alter chorea or cognitive dysfunction. Specific modulatory effects of glycine on the NMDA subtype of glutamate receptors, rather than the AMPA receptors, which may predominate among target neurons of the subthalamus, may explain the therapeutic failure of milacemide.
Giuffra
M E
ME
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Mouradian
M M
MM
Chase
T N
TN
D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D005260:Female; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D009435:Synaptic Transmission / Q000187:drug effects
D000081:Acetamides; D005971:Glutamates; D008996:Monoamine Oxidase Inhibitors; C039332:milacemide; D018698:Glutamic Acid