by Ndidi Ngwuluka

Created on: December 25, 2008

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Although the cause of PD is not known, genetic and environmental factors are strongly considered to be the main determinants and also family history is a risk factor. Studies strongly suggest that exposure to pesticides, well water consumption, rural living, anonnacin (a sour-sop component) and other chemicals such as a synthetic opiate, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are some of the predisposing environmental factors leading to Parkinson's disease. These factors trigger a complex of pathogenic events which lead to death of neurons called the dopaminergic nigral neurons in the brain.

These neurons produce a chemical known as dopamine responsible for transmitting signals within the brain to ensure muscle activity by inhibiting muscle contraction while another chemical acetylcholine stimulates muscle contraction. When there is loss of dopaminergic neurons, there is decrease in dopamine which then permits the pronounced effect of acetylcholine. Hence PD is initiated as a result of deficient dopaminergic neurons which lead to an imbalance in muscle activity.

The four main symptoms of PD observed clinically are resting tremor, rigidity, bradykinesia (extreme slow movement) and gait disturbance with postural instability. Presently, there is no cure for PD. However there are several medicines used in the management of PD which provide relief from symptoms. These medicines include levodopa, monoamine oxidase-B inhibitors such as selegiline, amantidine, anticholinergics such as orphenadrine, dopamine receptor agonists such as bromocriptine and catechol-O-methyltransferase (COMT) inhibitors such as entacapone. Of all these medicines, levodopa is the gold standard and the most effective medicine for superior symptomatic control of PD at the initial stages of the disease. This may be due to the fact that levodopa is converted to dopamine which is required at the dopamine receptors to counter the pronounced effect of acetylcholine. Dopamine is not administered directly because it does not cross the blood brain barrier (BBB). Hence its prodrug, levodopa is used which crosses BBB.

The exogenous administration of levodopa does not provide constant concentration of dopamine required at the dopamine receptors due to the short half life of levodopa. At the initial stage of the disease, the neurons are sufficient to provide constant dopamine concentration at the dopamine receptor to ensure smooth muscle activity. These neurons convert levodopa to dopamine and are still able to store, release, reuptake, recycle it, as well as being able to autoregulate large amounts of dopamine to maintain constant dopamine concentration. However, as the disease progresses, more neurons are lost and the conversion of levodopa to dopamine is taken over by non-dopaminergic neurons such as glial cells. They only convert levodopa to dopamine and release it but they do not store, recycle or autoregulate the amount of dopamine released. Furthermore the dopamine receptors depend increasingly on the peripherial availability of levodopa. These give rise erratic fluctuations of dopamine which in turn lead to increased side effects experienced by PD patients after 3 to 5 years of chronic levodopa therapy.

Presently, levodopa is the best option for the management of PD until a means to stop the degeneration of dopaminergic neurons is found.

Learn more about this author, Ndidi Ngwuluka.
Click here to send this author comments or questions.