Six patients with idiopathic Parkinsonism were treated with a combination of amantadine and L-dopa and after 12 to 24 weeks amantadine was replaced by placebo for a six week period in a double-blind trial. Although there was a tendency for clinical disability ratings and scores on objective ratings of motor skills to deteriorate initially after amantadine removal, there was no significant deterioration in clinical improvement or motor performance during the period of amantadine withdrawal. Amantadine withdrawal also failed to cause any significant change in plasma concentrations of L-dopa or its metabolite 3-methoxy-dopa in these patients. In a group of 27 patients seen regularly as outpatients measurements of plasma L-dopa failed to correlate significantly with either oral dose or with clinical improvement scores. The plasma concentration of 3-methoxy-dopa, however, was on average 2.8 times higher than that of L-dopa, and there was a significant correlation between plasma levels of this metabolite and clinical improvement. It is suggested that 3-methoxy-dopa may contribute significantly to the therapeutic actions of L-dopa in Parkinsonism.
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