Actions of Levodopa and Dopamine in the Central Nervous System

In 1958, Carlsson1suggested that dopamine (3-hydroxytyramine; 3,4-dihydroxyphenethylamine) is intimately involved in the control of motor functions. This view has since been amply supported by neurochemical, pharmacological, and neurological evidence. The role of dopamine was deduced in the first place from its high concentrations in the basal ganglia of the brain and certain associated structures. This pointed to some independent physiological activity of the amine in the brain. Dopamine has weak pharmacodynamic actions in biological assay systems devised originally to study the actions of norepinephrine and epinephrine, and this fact seemed to exclude it from any important role peripherally, except as a biochemical intermediate. In 1961, initial clinical trials of the acute effects of levodopa in patients with Parkinson's disease in Montreal2and Vienna3revealed the potent neuropharmacological actions of this amino acid, fully demonstrated in 1967 by Cotzias and his colleagues. Developments in the biological and