Dopamine Replacement in PD
Levodopa was developed over 50 years ago in the 1960s many years after James Parkinson in 1817 wrote about a constellation of symptoms that today we know as Parkinson’s disease. Decades later levodopa is still the gold standard treatment for the treatment of this chronic illness.
When taken orally, levodopa is absorbed into the blood from the small intestine. It then crosses the blood-brain barrier and is converted to dopamine by enzymes in the brain thereby helping to replace the neurotransmitter that has been lost as the brain’s own dopamine - producing neurons die.
Levodopa is almost always combined with the drug carbidopa, which helps prolong its effectiveness and prevents the medication from being broken down in the bloodstream before it reaches the brain. Instead of the high doses initially required, the addition of carbidopa allows the levodopa to be given in smaller doses thereby reducing the nausea and vomiting which can be a debilitating side effect. (In Europe, levodopa is combined with a different compound – benserazide with similar effect (brand name, Madopar)
Dopamine replacement therapy works exceptionally well in controlling the motor symptoms and helps improve the daily functioning of those affected by Parkinson’s. However it can also cause significant side effects such as dyskinesias (significant, bothersome involuntary movements), which may limit the amount of medication that can be used. This results in most people being under - dosed in terms of the amount of dopamine replacement they can tolerate –at times the side effects being worse than the original symptoms being treated. Additionally, it does not address the nonmotor symptoms of Parkinson’s, which are known to cause the majority of disability in patients.
Side effects of dopamine replacement therapy include, but are not limited to, nausea, vomiting, low blood pressure, lightheadedness, and dry mouth and in some individuals it may cause confusion and hallucinations. In the long-term, use of dopamine replacement can also lead to dyskinesias and motor fluctuations, i.e. more “off” periods when the medication isn’t working well.
Dopamine replacement comes in a variety of formulations and combinations. The more common preparations are as follows.
Levodopa/carbidopa comes in a short-acting form (Sinemet) as well as a long-acting one (Sinemet CR), the drug of choice depending on patient preference with the latter medication only requiring twice daily dosing. Levodopa/carbidopa comes also in an orally disintegrating tablet (Parcopa) that doesn’t require water to take and is helpful for those with swallowing difficulties.
Levodopa/carbidopa/entacapone (Stalevo) is another long - acting preparation of dopamine replacement that in addition to levodopa and carbidopa has added medication entacapone, which further prolongs the effectiveness of this formulation allowing for longer dosing periods.
Currently only available in Canada and Europe, levodopa/carbidopa gel (Duodopa) is a form of dopamine replacement that is delivered directly into the small intestine via a surgically placed tube. It is best used for individuals with advanced disease who are unable to gain control over their disabling motor symptoms with other available medications. By using a pump system akin to the insulin pump in diabetes, Duodopa is able to deliver the medication continuously throughout the day.
The popular saying “old is gold” certainly rings true when it comes to levodopa.
Despite the advances in the field of Parkinson’s disease research, no other new drug has shown to be as effective as levodopa in terms of relieving the motor symptoms of this disease. However side effects, particularly the long - term ones involving motor fluctuations and dyskinesias, limit its true effectiveness as an ideal treatment.