A brief history of levodopa
1913, Dr. GUGGENHEIM
Dr. Guggenheim felt sick. He noticed that his pulse was racing and he had to vomit. He thought, and rightly so, that it was because he had eaten too many beans.
He had the idea of analyzing them in his laboratory and then learned that he had discovered a new amino acid, dihydroxy-phenylalanine or levodopa (1). It was unevenly deposited in the plant, the pods containing more than seeds. This happened in 1913.
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​LEVODOPA IS CONVERTED TO DOPAMINE
From the biological point of view levodopa was apparently inactive. A growing interest in 1938 followed the discovery of an enzyme, decarboxylase, which turns levodopa into dopamine, the first active amine in the chain of catecholamines.
PARKINSON'S PATIENTS LACK OF DOPAMINE
Hornykiewicz, from whom I copy the title of this chapter (2) made ​​several findings around 1960: the brain of Parkinson’s patients, particularly the basal ganglia, contains greatly decreased amounts of dopamine (3), which is a neurotransmitter essential for motor coordination.
DOPAMINE INCREASED AFTER TAKING LEVODOPA
The next step, after an initial hesitation, was to try oral administration of levodopa. It was found that dopamine ascended to the brain and that people with Parkinson's disease improved dramatically: the shaking stopped and their walking improved miraculously. But there was a serious problem, their nausea and discomfort were hardly endurable.
BEGINNING TO WALK, THEY BEGAN TO VOMIT
I was a child when my father, a great doctor in a small village (beautiful Almuñécar), so proud of his profession, showed me Larodopa, the medication given him by a delegate from Roche Laboratories.
"This makes walking some who are paralyzed by Parkinson's disease, although it provoked vomiting and they feel very bad."
Larodopa contained only synthetic levodopa. After crossing through the duodenum to the blood, levodopa reaches the brain, and allows the parkinsonian to walk. However, it also reaches the intestine, heart and other organs, causing vomiting, tachycardia, and an overall sorry state.
That memory never faded and I found a miracle when I saw people paralyzed for years who, when beginning to walk, began to vomit.
SINEMET AND MADOPAR PREVENT VOMITING
Dopamine (not levodopa) improves the symptoms of Parkinson's disease. We need to increase dopamine in the brain since it improves the rigidity and tremor, but it it is preferable that the dopamine not remain in the blood or the rest of the body because it can cause vomiting, tachycardia, and other uncomfortable symptoms.
To prevent vomiting and other ailments Sinemet (from Latin sine and emetere words: without vomits) came to the fore. The trick was to add another substance to the levodopa, carbidopa, which inhibits decarboxylase (it destroys the destroyer) and prevents levodopa from being converted to dopamine.
As carbidopa does not cross the blood-brain barrier, it does not affect brain dopamine, but it inhibits the formation of dopamine in the blood. That way the brain receives the benefits of dopamine and other organs do not suffer damage.