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Monday, 2 February 2009

Levodopa (L-dopa): a treatment for Parkinson's disease

Parkinson’s disease is a degenerative disorder of the central nervous system. It is characterized by tremor, muscle rigidity, a slowing of physical movement (bradykinesia) and a loss of physical movement (akinesia). It also associates with non-motor symptoms, such as thinking or behaviour disorders.

Dopamine depletion is typical in people with Parkinson, so dopamine was tried as a treatment for Parkinson’s disease. It was first synthesized in 1910, but as it does not cross blood-brain barrier, it could not reach its site of action.

Levodopa (a precursor or dopamine) was then used instead. L-dopa decarboxylase (which converts levodopa to dopamine) was used clinically in combination with levodopa. But much of levodopa was broken down to dopamine before reaching the brain and hence there were still problems with the amount of dopamine reaching its target. At the same time, dopamine released outside its target area caused major side effects. Hence, decarboxylase inhibitors were used to delay the conversion to dopamine until it reaches the brain.

To improve the efficacy of levodopa without the symptom fluctuationsand dyskinesias, dopamine agonists were developed. At first dopamine agonists were combined with levodopa; with a growing trend to use dopamine agonists at the early stage of treatment. Patients on dopamine agonists are less likely to develop dystonia and motor fluctuations than those on levodopa. But non-motor side effects (e.g. oedema, constipation, dizziness, and hallucinations) are more common on dopamine agonists.

Dopamine is converted to 3-O-methyldopa by catechol-O-methyl transferase (COMT). Hence, COMT inhibitors can improve the levodopa availability by improving the half life of dopamine. Entacapone (a COMT inhibitor) combined with levodopa and carbidopa (a decarboxylatase inhibitor) is considered as an effective combination.

Overall the choice of treatment should be individualized to each patient on the basis of clinical & lifestyle characteristics and patient preference.

Extracted from:
Jenny Bryan (2009). Levodopa_still the gold standard after 40 years of successful treatment. Pharmaceutical Journal, 282 (7537): 113-114

Disclaimer: the main purpose of this blog is to assemble my notes for my Continuing Professional Development (CPD). The topic discussed here should not be referred to as the only source of information. If there is anything with respect to this article that concerns you, please contact your doctor or pharmacist.

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