The Story of Levodopa: A Long and Arduous Journey

Levodopa (L-dopa) is the gold standard in the management of Parkinson's disease (PD). It dates back to 1500 to 1000 BC when it was used in the Indian Ayurvedic and Chinese system of medicine. Certain beans such as velvet beans and broad beans contain L-dopa. The plant Mucuna pruriens (Mp) or velvet bean, cultivated in Eastern India and Southern China, contains L-dopa at a concentration of 5% and was used for the management of PD. Later, workers have documented the neuroprotective, neurorestorative, and immunomodulatory properties of Mp. Double-blind studies conducted in the Western world have proved the efficacy of Mp and reported some toxic side effects as well. In the Western world, the credit for isolating L-dopa from the seeds of Vicia faba or broad bean goes to Markus Guggenheim, a biochemist from Sweden in 1913. However, it has been used with success ever since Arvid Carlsson established the reversibility of reserpine-induced akinesia in rabbits in the late 1950s with the use of intravenous dopamine, and Oleh Hornykiewicz demonstrated its deficiency in the striatum in 1960-1961. George Cotzias used it in patients in a low and slow incremental fashion in 1967, and Melvin Yahr and his colleagues performed double-blind study on in-patients with success in 1969. Complications with its long-term use, particularly the on-off phenomenon, and dyskinesias appeared soon, and measures have been undertaken to reduce their incidence. Researches on alternative modes of delivery are carried out in various centers, and others are under investigation in the laboratories.