Dopamine Replacement Therapy in Parkinson's Disease

Why Doctors Continue to Rely on Levodopa in Parkinson's Treatment

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Molecular model of levodopa. Pasieka / Science Photo Library / Getty Images

Levodopa is considered the gold standard for dopamine replacement therapy in Parkinson's disease. The medicine was developed in the 1960s many years after James Parkinson in 1817 wrote about a set of symptoms that today we know as Parkinson’s disease. Decades later, levodopa is still the most commonly used treatment of this chronic illness. 

When taken by mouth, levodopa is absorbed into the blood from the small intestine.

It is then converted to dopamine by enzymes in the brain, which helps to replace the neurotransmitter that has been lost as the brain’s own dopamine-producing neurons die.

How Levodopa Works

Levodopa is almost always combined with the drug carbidopa (like in the brand name drug Sinemet), which helps prolong levodopa's effectiveness and prevents the medication from being broken down in the bloodstream before it reaches the brain. Instead of the high doses initially required, the addition of carbidopa allows the levodopa to be given in smaller doses. This reduces nausea and vomiting, often debilitating side effects. In Europe, levodopa is combined with a different compound called benserazide with similar effect in the brand name drug Madopar.

Dopamine replacement therapy works exceptionally well in controlling the motor symptoms and helps improve the daily functioning of those affected by Parkinson’s.

However, it can also cause significant side effects such as dyskinesias (bothersome involuntary movements), which may limit the amount of medication that can be used. This results in most people being underdosed as far as the amount of dopamine replacement they can tolerate. At times, side effects are worse than the original symptoms being treated.

Additionally, it does not address the nonmotor symptoms of Parkinson’s, which are known to cause the majority of disability in patients.

Levodopa Side Effects

Side effects of dopamine replacement therapy include, but are not limited to, nausea, vomiting, low blood pressure, lightheadedness, and dry mouth. In some individuals it may cause confusion and hallucinations. In the long-term, use of dopamine replacement can also lead to dyskinesias and motor fluctuations (i.e., more “off” periods when the medication isn’t working well).

Types of Dopamine Replacement Therapies

Dopamine replacement therapy comes in a variety of formulations and combinations. The more common preparations are as follows:

Levodopa/Carbidopa: This combination comes in a short-acting form (Sinemet) as well as a long-acting one (Sinemet CR) which only requires twice-daily dosing. Levodopa/carbidopa also comes in an orally disintegrating tablet (Parcopa) that doesn’t require water to take and is helpful for those with swallowing difficulties.

Levodopa/Carbidopa/Entacapone: Stalevo is another brand name long-acting preparation of dopamine replacement that in addition to levodopa and carbidopa has the added medication entacapone, which further prolongs the effectiveness of this formulation allowing for longer dosing periods.

Currently only available in Canada and Europe, levodopa/carbidopa gel (Duodopa) is a form of dopamine replacement that is delivered directly into the small intestine via a surgically placed tube. It is best used for those with advanced disease who are unable to gain control over their disabling motor symptoms with other available medications. By using a pump system similar to the insulin pump in diabetes, Duodopa is able to deliver the medication continuously throughout the day.

The popular saying “old is gold” certainly rings true when it comes to levodopa. Despite the advances in the field of Parkinson’s disease research, no other new drug has shown to be as effective as levodopa in terms of relieving the motor symptoms of this disease. However, side effects, particularly the long-term ones involving motor fluctuations and dyskinesias, limit its true effectiveness as an ideal treatment.

Sources:

Parkinson's Disease Clinic and Research Center. Parkinson's Disease Medications. UCSF, 2014.

"Prescription Medications." - Parkinson's Disease Foundation (PDF). Parkinson's Disease Foundation, n.d.

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