A Review of Levodopa: The First Line in Treating Parkinson’s Disease

by Shailen Sampath
Edited by Ashley Nee

10 million people worldwide suffer from Parkinson’s disease (PD), a nervous system disorder that leads to progessive loss of motor function. It is unknown what PD itself is caused by; however, a lack of production of the neurotransmitter dopamine is widely accepted as a part of the disease pathology. This lack of dopamine leads to cell death in areas of the brain involved in movement, such as the substantia nigra. In a testament to the brain’s plasticity, the brain is able to compensate for this lack of dopamine production, often allowing PD to remain undiagnosed and untreated in patients for years. Following diagnosis, several treatment options - none of which are curative - are available. These treatments focus on reducing the disease’s major symptoms, such as impaired movement, and improving the quality of patients’ lives. [1]

Carbidopa enhances the effects of Levodopa and is therefore often used in combination with Levodopa treatment. Source of picture: https://www.sunpharma.com/node/120442

Dopamine targeting drugs allow patients to temporarily improve their basic motor function. Levodopa is the first line drug treatment that is prescribed to all patients, regardless of the severity stage of the disease. Levodopa, upon introduction to a patient’s system, is absorbed by the intestines and transported to the brain through the bloodstream, where it is then converted into dopamine. Increased levels of dopamine in the brain allow patients to regain some motor function and partake in normal daily activities. Unfortunately, this improvement in function comes at a cost.

Patients who take levodopa eventually experience tremors, or dyskinesia, as the effects of the drug subside over time. While the exact mechanism for these tremors remains an area of continued research, levodopa induced dyskinesia is a major struggle for PD patients. People have described the drug’s effects to be like a yo-yo, as the symptoms of dyskinesia disappear once they take levodopa and then reappear right before they are ready to take their next dose. Every year, of the patients using levodopa, 10% develop motor fluctuations, and 50% suffer from these complications after 5 years of using levodopa. [2] Today, physicians address levodopa induced dyskinesia by adjusting the amount of drug administered based on a patient's symptoms.

​Levodopa is offered in various forms in order to help reduce the level of tremors that a patient experiences. However, finding an optimal dosage of levodopa remains a significant challenge. As researchers strive to better understand the underlying mechanism of PD, finding ways to diminish levodopa induced dyskinesia will remain one of the largest focuses in the treatment of patients living with PD. From smart wearables to digital artificial intelligence software, there are many innovations today, which track tremors, that aim to make drug dose selection a more efficient process. [1] 

Citations
[1] Asaad, Wael F. 8 Oct. 2019.
[2] Schrag, et al. “Dyskinesias and Motor Fluctuations in Parkinson's Disease: A Community-Based Study.” OUP Academic, Oxford University Press, 1 Nov. 2000, academic.oup.com/brain/article/123/11/2297/256050.

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