Levodopa, Involuntary Movements and Fusaric Acid

To the Editor.— Levodopa is now generally accepted as the most effective therapy for the symptoms of parkinsonism1-4although it can induce involuntary movements which can mar some of its most dramatic responses.1In our hands, control of these movements without cancellation of the therapeutic effects has been achieved for minutes only, following injections of apomorphine.5Since all other attempts to control these movements have invariably caused reemergence of parkinsonism, we have proposed that the underlying mechanisms are unknown.6 This situation called for the formulation of a hypothesis which might at least lead to novel experiments. Our hypothesis is presently this: Since levodopa generates cerebral dopamine as a necessary step in its therapeutic action,6the norepinephrine synthesized from dopamine might be causing the involuntary movements. The synthesis of cerebral norepinephrine from administered levodopa proceeds as follows: levodopa becomes decarboxylated widely in the brain to generate