Dopamine Agonists

 

On 7 November 2006, The Medicines and Healthcare products Regulatory Agency (MHRA*) published a Public Assessent Report on dopamine agonists and pathological gambling, increased libido and hypersexuality. The report summarises a review by the Phamacovigilance Working Party (PhVWP) of the European Committee for Medicinal Products for Human Use (CHMP) and recommends that the product information for all dopamine agonists is updated to warn that pathological gambling, increased libido and hypersexuality are potential class effects of treatment with dopamine agonists for Parkinson's disease.

Patients should seek help from their doctor if they, their family, or their carer, notice that their behaviour is unusual.

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* The Medicines and Healthcare products Regulatory Agency (MHRA) is the UK government agency responsible for ensuring that medicines and medical devices work, and are acceptably safe.

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Unlocking Doors By Copying Keys

Dopamine receptor agonists are drugs that have a structure very similar to dopamine. Because of this similarity, they are able to mimic the action of dopamine rather than replenish the inadequate supply of dopamine in the way levodopa does - unlike levodopa, they don’t need to be converted by the brain cells first.

If one imagines dopamine as being a key (agonist) which only fits a specific lock (receptor) to let a door open (body movement), losing the key to the door means that the door cannot be opened. The loss of dopamine therefore means that the receptors will not receive the signal telling the body to move properly. But because dopamine agonists have a similar structure to dopamine, they are able to fit into the dopamine receptor, resulting in the same signal being sent that occurs with dopamine in the non-diseased state and normal control of body movement is restored.

Dopamine agonists work by stimulating the parts of the brain (dopamine receptors) where dopamine works.

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Types of dopamine agonists

There are two types of dopamine agonists – ergoline and non-ergoline. These refer to the structure of the medication rather than its action. Ergot is a fungus that the first dopamine agonist medications were derived from. It has a very distinctive chemical structure that has been copied in laboratories to make ergoline dopamine agonist compounds. As well as acting on dopamine receptors, they may also have important effects on other chemical receptors in the brain.

Non-ergoline dopamine agonists are selective and work on specific dopamine receptors.

All of the dopamine agonists are taken orally in tablet or capsule form apart from apomorphine, which is injected, and rotigotine which is available as a transdermal patch.

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Side Effects

The main side-effects of dopamine agonists are nausea, vomiting, and a lowering of blood pressure caused by changes in posture (orthostatic hypotension). These are usually caused by the action of dopamine agonists at dopamine receptors found in other areas of the brain or body that are not involved in movement or Parkinson's.

To avoid such side-effects, the dose of dopamine agonists taken is usually increased slowly by the primary care physician until the appropriate dose is reached, signalled by the improvement of motor symptoms and hopefully without the emergence of side-effects. Alternatively, other medication may be prescribed to treat or minimize unwanted side effects from dopamine agonists or by decreasing the dose of the dopamine agonists medication. Other, more severe side-effects may include hallucinations and psychotic reactions.

Compared to levodopa, dopamine agonists have a slightly longer duration of action and may suit some people better than levodopa. Dopaminie agonists can be taken as initial therapy for newly diagnosed patients. In patients at a later stage of disease, whose response to levodopa therapy is no longer predictable, dopamine agonists can be given together with levodopa to ‘smooth out’ the control of symptoms. Your doctor must carefully weight the pros and cons of the different treatments available and tailor your therapy according to your needs in order to provide you with the best Parkinson's symptom control possible without causing disturbing side effects.

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Further reading on Dopamine Agonists