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07_Parkinsons - Treatment of Parkinsonism With Some turn...

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Treatment of Parkinsonism With Levodopa Melvin D. Yahr, MD; Roger C. Duvoisin, MD; Myrna J. Schear, MD; Robert E. Barrett, MD; and Margaret M. Hoehn, MD, New York Some turn this sickness yet might take, Even yet. But he: "What drug can make A wither'd palsy cease to shake?" "The Two Voices" \p=m-\Tennyson 1833 FOR MORE than a century, the treat- ment of parkinsonism has relied on a vari- ety of compounds whose limited therapeutic efficacy depend upon their central parasym- patholytic effects. The shortcomings of these agents, notably their inability to com- pletely reverse the signs and symptoms or materially alter the progressive disabling na- ture of the disorder and the high incidence of disturbing side effects, are well appreciat- ed. Under the most optimal circumstances, the best that can be expected from their judicious administration is a 20% reduction in the severity of symptoms with a modest improvement of functional capacity. The demonstration within the past decade of the presence of dopamine in the brain localized chiefly in the striatum and substantia nigra1,2 and the subsequent discovery of its depletion in parkinsonism3,4 and in labora- tory animals following nigral lesions5·6 have provided the rationale for new therapeutic approaches to parkinsonism. Among the several means considered for correcting the dopamine deficiency, the administration of levodopa, the immediate precursor of dopa¬ mine, has proved, thus far, the most effective, and we believe it to represent a major ad¬ vance in the treatment of parkinsonism. The initial observations on the effects of levodopa in parkinsonism were made with single relatively small oral or parenteral doses. Using a technique previously em¬ ployed by Degkwitz,7 Birkmayer and Hornykiewicz8 administered doses of the order of 25 to 150 mg by slow intravenous injection and observed improvements of gait, speech, and bodily movement, which they interpreted as a decrease of akinesia. Tremor and rigidity did not appear to be significantly influenced. The "dopa effekt," as it was termed, reached its maximum in two to three hours and persisted to a lesser extent for 24 hours or longer. Barbeau,9·10 utilizing oral administration of 200 mg of levodopa in six patients, noted improve¬ ments in the performance of specific tasks of motor function which he interpreted as reduction of rigidity. Tremor was worsened in one case and remained unchanged in the remainder. Subsequently, Friedhoff et al,11 Gerstenbrand et al,12 Umbach and Bau¬ mann,13 and others14·15 reported essentially similar results using small oral or parenter¬ al doses of levodopa. Birkmayer and Hornykiewicz16 extended their studies and developed a therapeutic regimen in which slow intravenous injec¬ tions of levodopa repeated two or three Submitted for publication May 7, 1969; accepted June 6.
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