Levodopa - Parkinson's

Introduction[edit | edit source]

The mainstay of current PD treatment are levodopa-based preparations, designed to replace the dopamine in the depleted striatum. Dopamine itself is unable to cross the blood brain barrier (BBB) and cannot be used to treat PD. In contrast, the dopamine precursor levodopa is able to cross the BBB and can be administered as a therapy. After absorption and transit across the BBB, it is converted into the neurotransmitter dopamine by DOPA decarboxylase

The primary use of Levodopa is to restore depleted levels of dopamine at the presynaptic terminal of the substantia nigra, which restores functional movement[1]. This replacement can relieve symptoms of PD, such as freezing and rigidity[2].

Generally, the clinical effect of levodopa is noticed quickly, and may last for several hours, particularly in the early stages of disease. However, as disease becomes more advanced, the effect of the drug usually wears off after shorter durations, and an increased frequency of dosing is often required.

Levodopa comes with significant side effects that constitute an important part of the illness experienced by the patient, particularly in advanced disease. Some of its associated side effects result from the conversion of levodopa to dopamine outside the CNS (peripheral conversion) by DOPA decarboxylase. To reduce these side effects, levodopa is administered in combination with DOPA decarboxylase inhibitors such as benserazide and carbidopa. These compounds do not cross the BBB, but selectively prevent the peripheral conversion of levodopa to dopamine, thereby reducing the peripheral side effects. The most frequently prescribed combination drugs are carbidopa/levodopa (co-careldopa [trade names Sinemet, Pharmacopa, Atamet]) and benserazide/levodopa (co-beneldopa [trade name Madopar])[3]

Researchers continue to focus on the development of other long-acting oral preparations as well as other modes of drug delivery, which may allow for improved clinical efficacy and side-effect profiles in the future.[3]

References[edit | edit source]

  1. Lewitt MD, PA. Levodopa therapy for Parkinsons disease: Pharmacokinetics and pharmacodynamics. Movement Disorders. 2014;30(1):65-67. doi:10.1002/mds.26082.
  2. Connolly MD, BS, Lang MD, AE. Pharmacological Treatment of Parkinson Disease. Jama. 2014;311(16):1670. doi:10.1001/jama.2014.3654.
  3. 3.0 3.1 Zahoor I, Shafi A, Haq E. Pharmacological treatment of Parkinson’s disease. Exon Publications. 2018 Dec 21:129-44. Available:https://www.ncbi.nlm.nih.gov/books/NBK536726/ (accessed 14.4.2022)