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Typical Antiparkinsonian


First isolated in 1913, L-dopa was initially declared biologically inactive. Luckily for the 1.5 million people in the U.S. who suffer from Parkinson's disease, the legume-derived amino acid r eceived a second look. Since the early 1960s, L-dopa has been considered a gold-standard treatment for the disease. Over the course of almost 50 years, and from an inauspicious beginning, the history of L-dopa research paralleled scientific advances in understanding neurotransmitters, especially the role of dopamine in regulating central motor function.

L-Dopa (l-3,4-dihydroxyphenylalanine) was first isolated from seedlings of Vicia faba by Marcus Guggenheim in 1913. The faba, or broad bean, is a staple crop in some Asian and Mediterranean regions because of its high protein content of 20 to 25%. Guggenheim suspected that L-dopa was a precursor to adrenaline. To test this conjecture, he self-administered 2.5 g and noted its emetic action. After later experiments with rabbits, however, he concluded that it was not biologically active, and that was the prevailing opinion for almost 15 years.

Beginning in 1927, biochemists discovered that L-dopa was biologically active in rabbits, causing a fall in arterial blood pressure. In 1938, Peter Holz found that L-dopa decarboxylizes into dopamine in mammalian tissue. Experiments in the early 1940s demonstrated an increase in blood pressure in cats and humans caused by the formation of dopamine in the body. During the 1950s, medical researchers found L-dopa in many tissues of the human body, especially in the brain, and continued to investigate whether the compound is a precursor to adrenaline.

Also in the 1950s, research into the precursors of other catecholamines--naturally occurring compounds that serve as neurotransmitters in the sympathetic nervous system--was gaining momentum. At first, scientists were most interested in the formation of adrenaline-like substances, but by 1959, the role of dopamine in the regulation of central motor function and its reversal of Parkinson's-like conditions was discovered.

To mimic Parkinson's disease, researchers administered a "tranquilizing" drug called reserpine. Reserpine on its own was evaluated as an antipsychotic along with chlorpromazine (see also Thorazine) because dopamine uptake was shown to effect mood regulation.

The ways in which brain chemicals regulate human physical and mental well-being are still being studied and debated. For example, too much dopamine has been correlated with schizophrenia. To date, neurological researchers have identified more than 50 kinds of neurotransmitters. Because it is often very difficult to predict how different amounts of neurotransmitters affect human health, the discovery of L-dopa as a treatment for Parkinson's seems refreshingly straightforward.

IN THE BEGINNING L-Dopa was first isolated from Vicia faba seedlings. The aromatic amino acid is commonly found in plants and animals. SASKATCHEWAN INTERACTIVE PHOTO

IN THE BEGINNING L-Dopa was first isolated from Vicia faba seedlings. The aromatic amino acid is commonly found in plants and animals.

In 1960, a study by autopsy of the brains of people who'd had Parkinson's disease found severe dopamine loss. The very next year, two trials of L-dopa in patients with Parkinson's disease showed dramatic improvements in all motor deficits.

The L-dopa regimen as prescribed today is not much different from that developed in 1967 after six years of studies. Its mode of action is to replenish missing striatal dopamine in the brain. Parkinson's patients lose the ability to produce dopamine, resulting in a progressive loss of motor function. Symptoms include tremor, rigidity, slowness of movement, and impaired balance. Dopamine cannot be administered directly because it does not pass the blood-brain barrier; however, the body converts oral doses of L-dopa to dopamine by decarboxylation. Dopamine is then stored in the brain in vesicles in the presynaptic nerve terminals.

To counteract Parkinson's symptoms, L-dopa needs to be taken in large doses that typically must be increased over time. The drug has some serious side effects, including nausea and dyskinesias (involuntary movements). Carbidopa is often prescribed to delay the conversion of L-dopa to dopamine until it reaches the brain, lessening side effects.

In 1997, the Food & Drug Administration approved three new drugs to treat Parkinson's disease: Mirapex, Requip, and Tasmar. All three can be used along with L-dopa to improve symptoms and decrease L-dopa doses.

The history books are not yet closed on L-dopa. Neuroscientists are studying whether it is a neurotransmitter in its own right. It may regulate the amount of dopamine in the body and play a role in the regulation of blood pressure. One thing is certain: It won't likely be underestimated again.—MELODY VOITH


The Top Pharmaceuticals
That Changed The World
Vol. 83, Issue 25 (6/20/05)
Table Of Contents


L-Dopa structure


  • 3-Hydroxy-L-tyrosine

CAS Registry

  • 59-92-7

Other Names

  • L-Dopa
  • l-3,4-dihydroxyphenylalanine


1967, Hoffmann-La Roche

Did you know that William S. Knowles won the 2001 Nobel Prize in Chemistry for his work on the Monsanto synthesis of L-dopa using catalytic asymmetric hydrogenation?