What is the Difference Between Levodopa and Carbidopa

The key difference between levodopa and carbidopa is that levodopa is used as the primary medication to treat Parkinson’s disease and converts into a neurotransmitter called dopamine, while carbidopa is used as a cotreatment with levodopa to inhibit the conversion of levodopa to dopamine in the peripheral nervous system and to cure levodopa-associated dyskinesias.

Parkinson’s disease is characterized by decreased dopamine production due to the loss of dopaminergic neurons in the brain. Levodopa is the dopamine precursor, which L-dopa decarboxylase will convert into dopamine. The conversion of levodopa into dopamine due to the levodopa supplementation can occur even in peripheral neurons due to aromatic L-amino acid decarboxylase in the liver, kidneys, pancreas, and T lymphocytes. To prevent the conversion of levodopa to dopamine in peripheral tissues, carbidopa, an aromatic L-amino acid decarboxylase inhibitor, is cotreated with levodopa. Interestingly, carbidopa cannot cross the blood-brain barrier, indicating that the inhibitory activity of carbidopa is absent in the brain. Therefore, levodopa supplementation is an effective treatment for Parkinson’s disease.

CONTENTS

1. Overview and Key Difference
2. What is Levodopa 
3. What is Carbidopa
4. Similarities – Levodopa and Carbidopa
5. Levodopa vs Carbidopa in Tabular Form
6. Summary – Levodopa vs Carbidopa

What is Levodopa?

Levodopa [(-)-3-(3,4-dihydroxyphenyl)-L-alanine] is a dopamine precursor that is used to treat Parkinson’s disease. The aromatic L-amino acid decarboxylase enzyme regulates the conversion of levodopa to dopamine. Levodopa can readily cross the blood-brain barrier, and dopamine will be produced in the brain upon levodopa supplementation, which is effective in idiopathic Parkinson’s disease. In addition, the drug displays high levels of efficacy, tolerability, and low cost, making it a primary treatment in managing all stages of Parkinson’s disease. Aromatic L-amino acid decarboxylase is generally present in peripheral tissues such as the liver, kidney, and pancreas, and the supplementation of levodopa results in the systemic production of dopamine, limiting dopamine availability in the central nervous system.

Furthermore, the activation of peripheral dopamine receptors is shown to result in nausea and vomiting. Therefore, upon levodopa supplementation, a mechanism is needed to prevent the conversion of levodopa to dopamine by the aromatic L-amino acid decarboxylase enzyme.

What is Carbidopa?

Levodopa is often prescribed with an amino acid decarboxylase inhibitor to reduce the conversion of levodopa to dopamine in the peripheral tissues. In addition, treating levodopa is often associated with dyskinesias, and combining levodopa with carbidopa is recommended to alleviate dyskinesias conditions.

Carbidopa is a catechol-related compound that acts as an aromatic L-amino acid decarboxylase inhibitor. Carbidopa does not cross the blood-brain barrier, so the conversion of levodopa to dopamine will not affect the brain. Furthermore, recent studies on the mechanism of action of carbidopa revealed that carbidopa suppresses unnecessary activation of memory T cells in the central nervous system, which benefits individuals with Parkinson’s disease.

What are the Similarities Between Levodopa and Carbidopa?

• Levodopa and carbidopa are commonly prescribed as a combination therapy for Parkinson’s disease.
• Both medications work together to alleviate the symptoms of Parkinson’s disease, such as tremors, rigidity, slowness of movement, and postural instability.
• Levodopa and carbidopa are often available in combination formulations, where both medications are combined into a single tablet or capsule.
• They collectively increase dopamine levels in the brain.
• Both levodopa and carbidopa are prescription medications and, therefore, should be used under the supervision and guidance of a healthcare professional.

What is the Difference Between Levodopa and Carbidopa?

Levodopa and carbidopa are combined medications used to treat Parkinson’s disease but with different mechanisms of action. Levodopa is the main medication that is converted into dopamine to alleviate the symptoms. In contrast, carbidopa, combined with levodopa, inhibits the conversion of levodopa to dopamine outside the brain by inhibiting aromatic L-amino acid decarboxylase enzyme and reducing levodopa-associated dyskinesias. Thus, this is the key difference between levodopa and carbidopa. Levodopa acts as a dopamine precursor, increasing dopamine levels in the brain, while carbidopa enhances the efficacy of levodopa and helps manage side effects. Levodopa is available in various formulations, and carbidopa is combined with levodopa in combination formulations. Understanding the difference between levodopa and carbidopa is important for effective Parkinson’s disease treatment.

The infographic below presents the differences between levodopa and carbidopa in tabular form for side-by-side comparison.

Summary – Levodopa vs. Carbidopa

Although levodopa and carbidopa have distinct modes of action, they are used as combined medications to treat Parkinson’s disease. Levodopa is the primary medication that converts into dopamine, a neurotransmitter that alleviates disease symptoms. In contrast, carbidopa inhibits the conversion of levodopa to dopamine in peripheral tissues and reduces levodopa-associated dyskinesias. Therefore, receiving levodopa increases the dopamine levels in the brain, while carbidopa enhances the efficacy of levodopa and helps manage its side effects. Moreover, levodopa comes in various formulations, while carbidopa is typically coupled with levodopa in combination formulations. In addition, the side effects and dosage adjustments differ between the two medications. Levodopa is metabolized primarily by the aromatic L-amino acid decarboxylase enzyme, while carbidopa undergoes minimal metabolism. Therefore, it is crucial to comprehend the difference between levodopa and carbidopa for Parkinson’s disease treatment to be effective.

Reference:

1. Ertokus, Guzide Pekcan. “The Determination of Parkinson’s Drugs in Human Urine by Applying Chemometric Methods.” International Journal of Analytical Chemistry, vol. 2019, 2019, pp. 1–8.
2. Zhu, Huabin, et al. “Carbidopa, a Drug in Use for Management of Parkinson Disease Inhibits T Cell Activation and Autoimmunity.” PLOS ONE, vol. 12, no. 9, 2017.

Image Courtesy:

1. “3,4-Dihydroxy-L-phenylalanin (Levodopa)” By NEUROtiker – Own work (Public Domain) via Commons Wikimedia
2. “Carbidopa” By Fvasconcellos (talk · contribs) – Own work (Public Domain) via Commons Wikimedia