L-dopa

Dihydroxyphenylalanine, or levodopa, more commonly known as l-dopa, is an amino acid and medication that is widely used as a treatment for Parkinson’s disease, a detrimental neurodegenerative disorder². Its molecular structure, relatively short half-life, and long-term side effects create complications for those who seek to see it as a hope to treat an often life-threatening disease.

Figure 1. Molecules drawn with Notability, based on Neuroscientifically Challenged

Although l-dopa is a molecule that helps produce dopamine in the brain, both molecules differ slightly in their structure. Tyrosine, an amino acid that creates l-dopa in the brain, also has a similar structure. All three molecules comprise benzene rings with alkane and hydroxyl groups attached. Tyrosine is unique in that it only contains one hydroxyl group on the benzene ring, while l-dopa and dopamine contain two. Moreover, dopamine is the only molecule out of the three to lack a carboxylic acid group at the end, as it terminates with a simple NH2 group². Tyrosine, l-dopa, and dopamine all have carbons bonded by π bonds in the ring and σ bonds on the alkane. There are also lone pairs (nonbonding electrons) on each molecule’s oxygen and nitrogen atoms².

Figure 2. Carbidopa and Levodopa Medication5

In the bloodstream, l-dopa proceeds to the brain to produce dopamine. L-dopa interestingly has a half-life of one hour¹. L-dopa is converted into dopamine by the aromatic amino acid known as the decarboxylase enzyme¹. Since the 1970s, l-dopa has been administered along with carbidopa, an enzyme inhibitor that expands l-dopa’s half-life in blood to one and a half hours¹. In the time since then, there have been more enzyme inhibitors added to l-dopa medication to extend its half-life even further¹.

Figure 3. Brain imaging of healthy vs. diseased brain3

The primary property of l-dopa that dopamine lacks is the ability to cross the notorious blood-brain barrier. Parkinson’s disease, the disease which l-dopa treats, is a result of the death of dopamine neurons in brain regions like the substantia nigra and dopamine deficiency in the basal ganglia4. The brain uses l-dopa acquired from external medication to synthesize and produce more dopamine to compensate for the deficiency that has been shown to cause challenges with movement in patients with Parkinson’s⁴. Therefore, l-dopa’s unique power to cross the blood-brain barrier has provided a treatment that dopamine drugs cannot provide as dopamine cannot enter the brain from the blood, rendering dopamine drugs useless when it comes to replenishing dopamine in the brain.

Despite all the benefits that come with the use of l-dopa, there may be consequences of long-term treatment. For one, l-dopa is not only a treatment, not a cure, and will not completely halt neurodegeneration; its efficacy will decrease with time⁴. L-dopa has side effects, such as l-dopa dyskinesias, a condition that causes involuntary movements, uncontrolled muscle contractions, and more⁴. However, there is no doubting the profound impact that l-dopa treatment has had on the hundreds of thousands of people who live with Parkinson’s disease every year who rely on the molecule and seek comfort amidst their difficult conditions.

Work Cited

1. Abbott, A. Levodopa: The Story so Far. Nature 2010, 466 (7310), S6–S7. https://doi.org/10.1038/466s6a.
2. Haddad, F.; sawalha, M.; khawaja, Y.; Najjar, A.; Karaman, R. Dopamine and Levodopa Prodrugs for the Treatment of Parkinson’s Disease. Molecules 2017, 23 (1), 40. https://doi.org/10.3390/molecules23010040.
3. Neurodegeneration Imaging Group, King's College London. Brain Imaging Showing Loss in Serotonin Function as Parkinson’s Disease Progresses; 2019.
4. Neuroscientifically Challenged. 2-Minute Neuroscience: L-DOPA. www.youtube.com. https://www.youtube.com/watch?v=dwu17GTKihA&t=31s (accessed 2023-07-03).
5. Westminster Pharmaceuticals. Carbidopa and Levodopa Tablets, USP. https://www.wprx.com/wprx-products/carbidopa-and-levodopa-tablets (accessed 2023-07-02).