Carbamazepine in torsion in dystonia.
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Biomedical subjects
Publications and source records attributed to S Fahn.
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Twenty-three patients with Parkinson's disease participated in long-term, double-blind evaluations of the effectiveness and side effects of amantadine in combination with levodopa therapy. Sixteen patients completed the year-long study, which consisted of randomized crossover of amantadine and placebo before levodopa was begun and again after 5 and 11 months of continuous levodopa therapy. Initially, 16 of 23 patients (70 percent) had a favorable response to amantadine during the first crossover period. After 1 year of levodopa, at least eight of 16 patients (50 percent) responded favorably to amantadine compared with placebo. Some of the amantadine responders previously had been nonresponders, and vice versa. The response to amantadine was quantitatively similar in the responders even after the patients had been receiving levodopa therapy. Amantadine should be tried as a therapeutic agent in addition to levodopa for parkinsonism if more beneficial effect is desired, even if amantadine was previously ineffective in the same patient.
To test possible biochemical mechanisms by which L-tryptophan may reverse mental side effects of levodopa therapy in parkinsonism we administered levodopa, 250 mg per kilogram intraperitoneally, alone and with L-tryptophan, 500 mg per kilogram intraperitoneally, to rats pretreated with the peripheral dopa decarboxylase inhibitor, carbidopa (25 mg per kilogram). Rats were decapitated 0.5, 1, and 2 hours following amino acid injection and brain levels of amino acids, amines, and acid metabolites were determined. As expected, levodopa alone reduced tryptophan and serotonin and increased dopa and dopamine at the 1 and 2 hour intervals. Concurrent administration of L-tryptophan did not significantly alter the increased dopa and dopamine but did restore serotonin levels to within normal range at all time points. If similar events occur in parkinsonian patients, normalization of brain serotonin and not competitive reduction of brain dopa and dopamine may be the basis for the improvement in mental status.
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