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Drugs used for Parkinson’s disease can be divided into five main groups. Most of the medicines used to treat the disease have only been around since 1970, and if the last 30 years are anything to go by, the next 30 should provide us with many more options.

1 Drugs which replace dopamine
2 Drugs which mimic the action of dopamine
3 Drugs which inhibit the action of acetylcholine
4 Drugs which prevent the breakdown of dopamine
5 Others

1. Drugs which replace dopamine
These are the mainstay of treatment for Parkinson’s disease. Their names are Sinemet (Co-careldopa) and Madopar (Co-beneldopa). They come in many different strengths as tablets, capsules, dissolvable instant-action preparations or controlled-release formulae. Each one has a specific use in the treatment of Parkinson’s disease.

Both drugs are a combination of levodopa and a chemical known as a dopa decarboxylase inhibitor. Levodopa given by mouth is absorbed into the system and is eventually converted into dopamine within the nerve cells in the brain. It is then used by these cells, as naturally occurring dopamine would be, to send messages from one cell to the next. The function of the dopa decarboxylase inhibitor in each case is to make sure that as much of the levodopa reaches the target cells as possible by stopping it from being digested on the way. This helps to limit the side effects. Levodopa was originally used by itself, but this almost never happens now.

When someone first starts taking these drugs they may develop nausea and dizziness, and also constipation and dark staining of the urine. In a few cases, people taking the drugs may experience confusion, nightmares and hallucinations. These drugs are, however, very good at relieving the symptoms of Parkinson’s disease, and these rarer side effects should not put people off trying them.

Often pharmacists advise people to take these drugs with food, but Madopar and Sinemet are absorbed by the same system in the gut that absorbs protein. This means that if the drugs are taken at the same time as a heavy meal containing a lot of protein, such as red meat, chicken, fish, eggs or cheese, some of the effect of the drug can be lost. Sinemet or Madopar only need to be taken at the same time as food if nausea is a problem, and even then it is sometimes more beneficial to add a special anti-sickness drug called domperidone than to lose the effect of the drug.

A general rule to follow is that these drugs work best taken with a light meal or on an empty stomach between meals. The only exception to this rule is Madopar Controlled Release (CR). This drug floats on top of the stomach contents, so it should be taken after meals or on an empty stomach between meals. This absorption problem with protein does not mean that you should avoid protein in your diet. It is an essential part of a balanced daily intake. The advice usually given is that it is best to eat your main meal in the evening. This allows the medicine to work well during the day when you need to be active, then you can relax in the evening.

Large doses of Vitamin B6, such as those taken by women experiencing hormonal problems, can interfere with the action of levodopa given without a decarboxylase inhibitor. Some indigestion remedies may also interfere, so please check with your specialist, doctor or pharmacist if you are concerned.

In the long term, some other side effects can develop. The tablets can become less effective. They may appear to take longer to act on the symptoms at each dose and their effects can wear off suddenly (the on/off phenomenon). They can also cause involuntary twisting or writhing movements of the limbs or face called dyskinesias. Being very careful about when you take the drug helps to minimise this happening.

2. Drugs which mimic the action of dopamine
These are called ‘dopamine agonists’. Their names are as follows:

Parlodel (bromocriptine)
Celance (pergolide)
Revanil (lysuride)
Requip (ropinirole)
Cabaser (cabergoline)
Pramipexol (mirapex) 
Britaject (apomorphine) (injection)

Instead of trying to replace the missing dopamine, these drugs act directly on the receptor sites which dopamine stimulates, hence mimicking its action. They can be used on their own as treatment or in combination with Sinemet or Madopar. It is thought that using them early on their own may delay the need for levodopa and therefore prevent the long-term side effects of this drug. Each specialist has their own preference regarding treatment and eventually a combination of drugs is used to carefully control the symptoms. Each group of drugs can be very useful and has its place.

Agonists essentially have the same side effects as levodopa preparations. They are more likely to cause nausea and dizziness when they are first taken, so antisickness drugs may need to be given initially. Hallucinations, nightmares and confusion are also more common. Careful monitoring of the dosage should prevent these happening. A tiny dose is given to start with, and the dose is then slowly increased until the best effect is achieved.

Only one kind of dopamine agonist in tablet form should be taken at any one time. Some are taken once a day and others are taken three or four times a day. Food does not interfere with these tablets. They can be taken before, during or after meals. Apomorphine, the injectable agonist, can be used in combination with all the other drugs. If you have severe asthma, heart problems, stomach problems or vascular problems you must tell the doctor as these drugs could make them worse. This group of drugs is most often used with younger people but can be given to older people with caution. These drugs should never be stopped suddenly.

3. Drugs which inhibit the action of acetylcholine
These drugs are known as anticholinergics. The ones that are commonly used are as follows:

Artane (benzhexol)
Disipal (orphenadrine)
Cogentin (benztropine)
Kemadrin (procyclidine)

All of these are available in tablet form, some as a syrup and one as an injection. These drugs work by dampening down the effect of acetylcholine within the brain and the nervous system. They help to restore a balance between the chemical messengers within the basal ganglia of the brain.

This group of drugs can be used to help suppress tremor, although with limited
success. They are also used in the initial stages of treatment by some doctors and specialists to help delay the onset of side effects due to levodopa.

Common side effects of anticholinergics are a dry mouth and blurred vision, plus urine retention in males. Hallucinations and confusion can also occur. Anticholinergic drugs can also cause memory impairment in a significant proportion of people using them. Given this, they are rarely used in people over 70 and are used with caution and in small doses with people under that age. In men with prostate problems or people with glaucoma, this group of drugs can make those problems much worse. If your doctor or specialist decides to try this form of medication with you, he or she will have taken all of the above into consideration first.

4. Drugs which prevent the breakdown of dopamine
The most common drug in this group is selegiline (Eldepryl). It is what is known as a monoamine oxidase inhibitor or MAOI. Selegiline has been used since the mid 1980’s and it was initially hoped that it might stop the disease progressing. This, however, has proved not to be the case. In reality, because it stops the breakdown of dopamine, it gives a little relief from the symptoms of the disease. It is a mild anti-depressant and has a slight amphetamine effect, which means that it genuinely makes people feel better.

One research study has suggested that selegiline may be dangerous when taken long-term in combination with Madopar or Sinemet (co-beneldopa or cocareldopa). However, the findings of the research that led to this claim have not so far been reproduced elsewhere, and other papers suggest that it is not dangerous at all. Your doctor or specialist may have his or her own opinion about this and it is worth discussing the subject if you are concerned. Whatever dose of selegiline you are on, it should always be taken in the morning. If it is taken later it can interfere with sleep and cause restlessness or even nightmares and hallucinations. Selegiline should usually be stopped gradually where necessary.

COMT (catechol O-methyl transferase) inhibitors are a new variety of drugs that act to stop the breakdown of levodopa and dopamine, so prolonging the action of Sinemet and Madopar. Tolcapone (Tasmar) is already available and Entacapone should follow shortly. They will be a useful addition in the treatment of Parkinson’s disease, especially for people in the later stages of the disease, when Sinemet, Madopar or dopamine agonists stop working as effectively.

These drugs should always be taken in combination with Sinemet or Madopar. Usually the dose of Sinemet or Madopar will be reduced when the Tolcapone or Entacapone is added, but not always. Since this group of drugs can occassionally cause alteration in a person’s liver function the doctor will probably want to check regular blood samples for the first few months. Also this group of drugs may cause diarrhoea; if this is the case let your doctor or specialist know.

5. Others
Amantidine (Symmetrel) was originally developed as an anti-viral drug and by coincidence was found to help the symptoms of Parkinson’s disease. It is thought that it works by bypassing the need for dopamine in a similar way to dopamine agonists, but the target receptor sites it uses are different. It does not help everyone and only works for a limited length of time in those cases where it does have an effect. Because of how it works it is particularly useful in treating Parkinsonism, but it can be used to treat Parkinson’s disease as well, particularly where dyskinesias are a problem. On the whole it is a mild, welltolerated drug that rarely causes side effects, although it can cause sedation, confusion,hallucinations, diarrhoea and ankle swelling in a few people when used at higher doses.

New drugs are being developed all the time and information becomes outdated very quickly - for example, several anti-dyskinesia drugs are currently being tested. Please keep yourself informed by speaking to your doctor or specialist.