Since the symptoms of Parkinson are due to a loss of dopamine in the brain, most research has focused on the development of what are known as 'dopaminergic' medications. These medications are intended to replace the lost dopamine, copy or 'mimic' its action or stop its breakdown.
Delivering dopamine to the brain
Because dopamine itself does not naturally cross into the brain, it is often administered as levodopa (or L- Dopa), which passes into the brain where it is transformed into dopamine. Levodopa is usually given as a tablet or capsule.
Levodopa is highly effective in controlling most symptoms of Parkinson. More than 30 years after its discovery it remains the cornerstone of Parkinson therapy, and a large majority of patients receive levodopa therapy.
Failure to respond to levodopa may suggest that the disorder is not typical Parkinson, but a Parkinson like disorder, and further medical assessments may be required.
Once in the body, levodopa is broken down by molecules called enzymes – this reduces the amount of medication that can reach where it is needed in the brain.
There are two main enzymes involved in the breakdown of levodopa: Peripheral dopa- decarboxylase (DDC) and catechol- O- methyltransferase (COMT).
Inhibiting these enzymes can prevent levodopa's breakdown, optimizing its availability in the brain and improving symptom control. Unfortunately the effectiveness of levodopa can decline after years of treatment.
Peripheral dopa- decarboxylase inhibitors
These block one of the two enzymes that remove levodopa before it can reach the brain
In the 1970s, peripheral dopa- decarboxylase inhibitor (DDC) was the first of these two enzyme inhibitors to be identified, soon after levodopa was introduced. Using a DDC inhibitor ensures that more of the levodopa medication reaches the brain and reduces some potential side effects, such as nausea and vomiting, which can occur when dopamine is present at high levels in the blood stream. There are two DDC inhibitor medications available: carbidopa and benserazide. Because of the superior benefit of taking levodopa with a DDCI, levodopa pills are now always formulated with either carbidopa or benserazide in the same pill.
These block the other principal enzyme that removes levodopa before it can reach the brain
In the 1990s, COMT inhibitors were developed. COMT inhibition provides extended and smoother exposure of levodopa to the brain. This can improve and lengthen the response to each levodopa dose, thus increasing the amount of time when the symptoms of Parkinson are well controlled. COMT inhibitors are available as separate pills, but recently have been formulated as a part of the levodopa/DDCI pill in order to provide improved efficacy without complicating the dosing regimen or increasing the number of pills taken.
Mimicking the action of dopamine
Dopamine agonists mimic the action of natural dopamine rather than replacing it in the way that levodopa does.
Because of the long-term treatment complications that can be associated with levodopa therapy, in some cases, some doctors may prefer to try a dopamine agonist first in order to save levodopa for the later management of Parkinson.
Dopamine agonists can be a beneficial therapy for use either alone (as 'monotherapy') or in combination with levodopa. However, with time levodopa therapy is usually required.
The approach of giving dopamine agonists first is not always favored, particularly when your doctor feels that it is important not to compromise immediate improvements in mobility and quality of life because of the risk of future complications. Ultimately, the choice of which Parkinson medication to give rests between you and your doctor.
Some people cannot tolerate, or respond poorly to dopamine agonists, and a levodopa preparation may be the preferred initial therapy. Some side- effects of dopamine agonists, such as nausea and low blood pressure, can be reduced by 'titrating' the drug, which means starting at a low dose and slowly increasing the dose until your symptoms are satisfactorily controlled.
MAO- B inhibitors
Reducing the breakdown of dopamine in the brain
Monoamine oxidase type B (MAO- B) is an enzyme that breaks down dopamine in the brain. MAO- B inhibitors can be used either alone (usually in the early stages of therapy because of their limited benefits) or with levodopa to reduce dopamine break down and amplify the effects of levodopa.
Non- dopaminergic treatments
Therapies to treat Parkinson that do not directly affect dopamine are known as non -dopaminergic approaches. These include the 'anti-cholinergic' drugs that inhibit the action of another 'neurotransmitter', acetylcholine. In a healthy brain there is normally a balance between dopamine and acetylcholine. In Parkinson, acetylcholine becomes relatively more active due to the loss of dopamine.
Anticholinergics can help to redress this balance, but are less effective than dopaminergic therapies.
Amantadine is another drug that may enhance dopamine release or block the activity of another neurotransmitter called 'glutamate'. It is most frequently used in the early stages of Parkinson or later on for the treatment of involuntary movements (known as dyskinesias), which may be induced by long- term levodopa therapy.