Long-term management of Parkinson’s disease using levodopa combinations

ABSTRACT

Introduction: Parkinson’s disease is a chronic, neurodegenerative disease. Its symptoms and course are heterogeneous. After several years of investigative drug studies, levodopa remains the most efficacious drug despite its long-term limitations. Consequently, research into new drug delivery modes is ongoing.

Areas covered: This review summarizes past and current advances of levodopa therapy with a focus on long-term patient management. Current research aims to increase drug bioavailability and to deliver it to the brain continuously. Reduced fluctuations improve drug efficacy and levodopa-associated motor complications. Less considered metabolic long-term consequences of levodopa are impaired methylation capacity and antioxidant defense. Both may contribute to disease progression and weaken physiological available human neuronal repair mechanisms.

Expert opinion: New developed formulations will improve pharmacokinetic and pharmacodynamic behavior. The authors suggest the regular supplementation with methyl group-donating and free radical scavenging substrates to weaken the metabolic consequences of chronic and high levodopa dosing. Many patients perform this nutrient supplementation in their diet already.

KEYWORDS:

• Levodopa
• oxidative stress
• homocysteine
• motor complications
• neuronal repair

Article highlights

• L-dopa was a revolutionary breakthrough for treatment of PD.

• Current research on L-dopa focuses on mechanisms to improve bioavailability and pharmacokinetics of L-dopa.

• Decrease of the death rate in PD patients was found during the first 15 years of L-dopa application.

• High L-dopa dosing may induce neuronal death due to secondary drug-induced nutritional deficiencies because of antioxidant defense and methyl group consumption.

• Enzymatic blocking of L-dopa degradation was a success story.

This box summarizes key points contained in the article.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This manuscript was not funded.