What is the role of dopamine in Parkinson's disease?

What are the mechanisms of Parkinson's disease?

Parkinson's disease is a neurodegenerative disorder that progresses differently depending on the patient.

The symptoms common to patients with Parkinson's disease are:

• Stiffness,
• Slowness of movements,
• Tremors.
  
  

It is characterized by the destruction of dopaminergic (i.e. dopamine-producing) neurons, involved in body movements control. When 50 to 70% of dopamine neurons are destroyed, motor symptoms appear.

What is dopamine? 

Dopamine is a neurotransmitter (a substance released by the brain), essential for controlling body movements, and especially “automatic” movements, such as facial expressions. The destruction of dopaminergic neurons therefore causes dopamine deficit in the brain, forcing the patient to think about the movements to be performed, when they used to be performed automatically.

Dopamine is also involved in pleasure and motivation. This may explain the episodes of apathy or disinterest experienced by patients.

What are the first signs of Parkinson's disease?

Parkinson's disease is a progressive disorder. Even before the onset of the first symptoms, more than half of dopamine neurons will already have disappeared. But the diagnosis is unfortunately often established only after the appearance of the first symptoms.

However, some warning signs may exist. The signs most often observed are, however, discreet.

They can include:

• Fatigue,
• Difficulty concentrating,
• Decrease in productivity for everyday tasks,
• Sometimes depression.
  
  

In addition, micrographia, or abnormally small or cramped handwriting, often comes before other warning signs of Parkinson's disease (motor disturbances, due to dopamine deficiency, hamper writing movements). This symptom is specific to the disease, but patients or those around them rarely notice it.

What are the treatments for Parkinson's disease?

Treatments prescribed for Parkinson's disease aim at restoring normal levels of dopamine in the brain.

The main treatments administered are:

• Dopamine precursors, which will be transformed into dopamine in the brain,
• Dopamine agonists (substances that act like dopamine),
• Substances that block the breakdown of dopamine or its precursor in the brain, in order to keep its high concentrations as long as possible.

Dopamine precursor: levodopa 

Levodopa is converted into dopamine in the brain. It is the standard treatment for Parkinson's disease and has the best efficacy / adverse effects ratio. In order for this molecule to have time to reach the brain, it is associated with a substance that inhibits its breakdown in the blood (carbidopa).

However, if levodopa has been taken for several years, it tends to cause involuntary movements, called dyskinesia. That is why, it is mostly prescribed for patients who have had the disease for several years or who cannot tolerate other treatments, but also for patients aged 70 and older.

For patients under 70, who are only at the onset of the disease, dopamine agonists are usually prescribed.

Dopamine agonists 

Dopamine agonists are prescribed in the following situations:

• Only at the onset of the disease for patients under 70,
• In combination with levodopa, to reduce its dose,
• When motor fluctuations appear.
  
  

In the brain, they act like dopamine and cause fewer involuntary movements than levodopa, but are often responsible for more numerous side effects, such as nausea and vomiting, dizziness on waking, drowsiness and sleepiness, hallucinations and delusional episodes.

In addition, in some patients, dopamine agonists, when dosed too heavily, can cause mood swings, sexual or food hyperactivity and sometimes gambling addiction.

It is therefore recommended that patients taking dopamine agonists should be seen by a psychologist, especially during the adjustment period.

Levodopa breakdown inhibitors

The role of levodopa breakdown inhibitors is to maintain higher levels of levodopa in the brain.

There are two types of them, depending on the enzyme they block:

• COMT inhibitors
• MAO-B inhibitors.
  

They are prescribed in combination with levodopa if the patient experiences motor fluctuations. However, MAO-B inhibitors can be prescribed on their own at the onset of the disease, when symptoms are still mild.

The side effects of MAO-B are mainly episodes of confusion, while those of COMT inhibitors are diarrhoea and involuntary movements.

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