Levodopa
[CAS# 59-92-7]

Identification

• Classification: Inorganic chemical industry >> Inorganic salt >> Metal halides and halides >> Metal chlorides and salts
• Name: Levodopa
• Synonyms: 3-(3,4-Dihydroxyphenyl)-L-alanine; L-3-(3,4-Dihydroxyphenyl)alanine; L-DOPA
• Protein Sequence: X
• Molecular Formula: C₉H₁₁NO₄
• Molecular Weight: 197.19
• CAS Registry Number: 59-92-7
• EC Number: 200-445-2
• SMILES: C1=CC(=C(C=C1C[C@@H](C(=O)O)N)O)O

Properties

• Solubility: Soluble 5 mM (water)
• Melting point: 295 ºC
• alpha: -11.7 º (c=5.3, 1N HCl)

Safety Data

• Hazard Symbols: GHS07;GHS08;GHS09 Danger
• Hazard Statements: H302-H315-H319-H335-H361d-H372-H411-H412
• Precautionary Statements: P203-P260-P261-P264-P264+P265-P270-P271-P273-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P318-P319-P321-P330-P332+P317-P337+P317-P362+P364-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Reproductive toxicity	Repr.	2	H361
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Reproductive toxicity	Repr.	2	H361d
Eye irritation	Eye Irrit.	2A	H319
Specific target organ toxicity - single exposure	STOT SE	2	H371
Reproductive toxicity	Lact.	-	H362
Respiratory sensitization	Resp. Sens.	1	H334
Skin sensitization	Skin Sens.	1	H317
Acute toxicity	Acute Tox.	3	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H411
Germ cell mutagenicity	Muta.	2	H341
Reproductive toxicity	Repr.	1B	H360
Reproductive toxicity	Repr.	2	H360

Discovory and Applicatios

Levodopa, also known as L-DOPA, is a naturally occurring chemical precursor to dopamine, an essential neurotransmitter in the brain. Its discovery dates back to the early 20th century, when it was first isolated from the seeds of the broad bean plant, *Vicia faba*. In 1913, Levodopa was synthesized for the first time by the Polish biochemist Casimir Funk, but its potential therapeutic applications were not realized until much later. During the 1960s, Levodopa gained attention as a treatment for Parkinson’s disease, thanks to the pioneering work of neurologists George Cotzias and Oleh Hornykiewicz. They demonstrated that administering Levodopa could replenish the brain's dopamine levels, offering significant symptom relief to Parkinson's patients.

Levodopa is converted into dopamine by the enzyme aromatic L-amino acid decarboxylase (AAAD) once it crosses the blood-brain barrier. Dopamine itself cannot cross this barrier, making Levodopa an essential prodrug for increasing dopamine concentrations in the brain. The discovery of this mechanism revolutionized the treatment of Parkinson’s disease, a neurodegenerative disorder characterized by the loss of dopamine-producing neurons. Parkinson's patients typically experience tremors, rigidity, and bradykinesia, all of which can be alleviated by Levodopa therapy, making it the gold standard for treatment. Levodopa is commonly administered in combination with carbidopa, a peripheral decarboxylase inhibitor that prevents the premature conversion of Levodopa into dopamine outside the brain, thereby increasing its efficacy and reducing side effects such as nausea and cardiovascular complications.

Beyond Parkinson’s disease, Levodopa has been explored in the treatment of other movement disorders, including Restless Leg Syndrome (RLS) and dystonia. Its ability to restore dopamine levels has been beneficial in managing symptoms of these disorders as well. Furthermore, Levodopa has been studied in the context of certain neuropsychiatric conditions, although its primary therapeutic use remains in the management of Parkinson’s disease.

In addition to its medical applications, Levodopa’s role as a precursor in the biosynthesis of catecholamines has made it a valuable tool in neurobiological research. It has been used to investigate dopamine pathways and the broader understanding of neurotransmitter systems in both health and disease. Research on Levodopa has contributed significantly to the understanding of neurodegenerative disorders and the development of new therapeutic approaches that target dopamine signaling.

The limitations of Levodopa therapy have also been a focus of research, particularly concerning its long-term use. Chronic administration can lead to motor complications such as dyskinesia (involuntary movements) and fluctuations in drug efficacy, known as the "on-off" phenomenon. Despite these challenges, Levodopa remains a cornerstone of Parkinson’s treatment, and efforts continue to optimize its use, including exploring alternative formulations like controlled-release versions and combination therapies to improve patient outcomes.

References

1979. Behavioral study on the interactions between trazodone and L-dopa. Pharmacological Research Communications, 11(3).
DOI: 10.1016/s0031-6989(79)80088-0

1979. Levodopa and dopamine analogs: melanin precursors as antitumor agents in experimental human and murine leukemia. Cancer Treatment Reports, 63(6).
URL: 466656

1979. Pharmacokinetics of bromocriptine during continuous oral treatment of Parkinson's disease. European Journal of Clinical Pharmacology, 15(4).
DOI: 10.1007/bf00618517