Until Levodopa (L-DOPA) was developed in the late 1960s, Parkinson’s was treated with a blur of mostly misguided treatments: electric shock therapy, surgery on different areas of the brain, bleeding, arsenic, morphine, and mercury. Dr. Parkinson recommended bloodletting from the neck and blistering of the skin while inserting pieces of burnt cork to cause infection. The side effects of these treatments were usually worse than whatever relief they gave.
Levodopa was first isolated in 1913 but thought to be biologically inactive until the 1960s when it became the gold standard for the treatment of PD symptoms. Levodopa was to Parkinson’s what the Beatles were to popular music. Since its FDA approval in 1970, Levodopa has revolutionized the management of Parkinson's disease symptoms. L-DOPA is metabolized into dopamine in the brain by an enzyme called aromatic L-amino acid decarboxylase (AADC). Dopamine cannot pass through the protective blood-brain barrier, but L-DOPA can. When L-DOPA is taken orally, a small amount passes into the brain and is converted into dopamine which may offer relief of some PD symptoms (tremors) for 2 - 4 hours.
However, the body presents many obstacles that limit the efficiency of oral L-DOPA therapy. AADC, exists outside the brain as well, which means that the majority of orally administered L-DOPA will be converted into dopamine before reaching the central nervous system. Therefore, L-DOPA is typically administered with an inhibitor of peripheral AADC, called Carbidopa. Carbidopa (or another AADC inhibitor such as benserazide in Europe) helps to preserve orally administered L-DOPA for conversion to dopamine in the brain. Sinemet is the brand name in the US for Levodopa and Carbidopa combined into one pill. Madopar, available outside the US, is levodopa with benserazide as the AADC inhibitor. Levodopa doesn’t cure, prevent, or stop the progression of PD but relieves some symptoms, mostly tremors, for some people.
Now for the bad news. There is a long list of possible Levodopa/Carbidopa side effect and their likelihood incases with long term use. 40% of users experience dyskinesia (involuntary, uncontrollable movements) motor fluctuations within 4 - 6 years. The pulsating effect of taking a number of levodopa pills every day that have an initial strong impact on the brain followed by a short half life is another problem. Lets see, I’ve taken 3 pills a day 365 days a year for 4 years. That’s 4380 brain shocks so far. Should I be worried yet? How many pills have you taken?
Are you experiencing any of these possible side effects: dyskinesia, hallucinations, mental and mood changes, confusion, depression, suicidal thoughts, worsening of tremors, fainting, dizziness, drowsiness, blurred vision, nausea, vomiting, dry mouth, loss of appetite, heartburn, diarrhea, constipation, muscle pain, numbness or tingly feeling, trouble sleeping. insomnia. strange dreams, skin rash, itching, headache, twitching, unusual strong urges and the list goes on. You get the picture.
A dermal patch, a subcutaneous pump, and controlled release tablets have been developed to deliver levodopa in a continuous regulated way without jolting the brain. Providing a more continuous and regulated supply of dopamine to the brain may result in improved control of PD symptoms and lessen side effects.
Currently most PD medications are taken orally. However, it takes time for oral medications to be absorbed by the body before they start to work. An inhaled powder form of levodopa, Inbrija, was approved by the FDA in December 2018. Self administered with an inhaler it reaches the brain faster than orally administered levodopa and provides rapid improvement of motor function to significantly reduce off time.
Levodopa is a protein building block so it competes for absorption with food. Therefore to be most effective Sinemet should not be taken until two hours after eating and one hour before. More Levodopa must be taken with time. Does it lose its effectiveness or is it because the disease gets worse or is it both. Several PWP friends have taken Sinemet for a long time (8+ years) and developed dyskinesia. They see it as a quality of life issue, take Sinemet and feel better now or prevent possible future problems. Many people experiment with dosage and timing. I know about 20 PWP who take Sinemet and only a few take it as prescribed by their doctor.
L-DOPA converted to dopamine is likely to remain the gold standard for the treatment of PD for the near future. According to the National Institutes of Health “Of all agents, L-DOPA although the oldest, remains the most effective. However, l-DOPA's efficacy in advanced PD is significantly reduced.” In other words, Levodopa may become less effective and cause problems with long term use but it is the best therapy we now have for treatment of early Parkinson’s. Be happy if it helps you but be careful.
