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.

Parkinson's disease (Pd) is a neurological disorder that is characterized by a progressive loss of movement control. For this reason, it is often referred to as a movement disorder. The reason underlying this loss of body control is the loss (degeneration) of special cells populating an area of the brain, called the substantia nigra, which controls body movement. These cells normally produce dopamine, a chemical messenger (neurotransmitter), which is essential for the brain to transmit signals from the substantia nigra to another part of the brain, the striatum. It is through this communication that the brain is able to co-ordinate and control body movement. As the disease progresses and the brain loses its ability to produce dopamine, the clinical symptoms of PD, such as tremor and rigidity, appear.

Unlocking Doors By Copying Keys

Dopamine receptor agonists (DAs) 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.

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. Thus, the loss of dopamine means that the receptors will not receive the signal telling the body to move properly. But because DAs have a similar structure to dopamine, they are able to fit into the dopamine receptor, therefore resulting in the same signal being sent that occurs with dopamine in the non-diseased state. This means that as long as DAs are being taken, normal control of body movement is restored.

There are several types of receptors for dopamine in the striatum, the D1 and D2 receptors being the most investigated. Similarly there are many different kinds of DAs, the difference lying in the amount of activity that they have for a specific dopamine receptor subtype. While some DAs are unselective and stimulate both D1 and D2 receptors (pergolide), others, such as bromocriptine and the most recently developed DAs, ropinirole and pramipexole, selectively stimulate the D2 receptor but not the D1 subtype. These variations affect not only how well they work in controlling the symptoms of PD, but also account for the difference in side effects that a patient may experience on one particular drug compared to another.

Side Effects

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

To avoid such side-effects, the dose of DAs 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, a drug such as domperidone, which prevents the stimulation of D2 receptors outside the brain, may be prescribed to treat unwanted side effects from DAs. Other, more severe side-effects may include hallucinations and psychotic reactions. These can often be minimized by decreasing the dose of the DA or by taking drugs such as clozapine.

Compared to levodopa, DAs have a slightly longer duration of action and may suit some people better than levodopa. DAs 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, DAs 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 PD symptom control possible without causing disturbing side effects.

Medication Info

Dopamine Agonists

Dopamine Agonists

Unlocking Doors By Copying Keys

Side Effects

Further reading