Two studies, one on UK patients and another on Italian patients suggest that two types of drug for treating Parkinson’s disease may be causing leaky heart valves (cardiac-valve regurgitation).
The drugs in question are the ergot-derived dopamine receptor agonists “pergolide” and “cabergoline”. Pergolide is sold under the brand name Permax (Eli Lilly) and cabergoline under the brand names Dostinex and Cabaser (Pfizer).
The two studies are published in today’s issue of the New England Journal of Medicine.
The UK study looked at records of 11,417 patients in the United Kingdom General Practice Research Database who were aged between 40 and 80 and had received antiparkinsonian medication between 1988 and 2005 and found 31 cases of cardiac-valve regurgitation.
Of the 31 patients with newly diagnosed cardiac-valve regurgitation 6 were taking pergolide and another 6 were taking cabergoline up to 12 months previously. The ones on pergolide were 7 times more likely to have leaky heart valves, and the ones on cabergoline, 5 times. The ones on other types of dopamine agonists did not show this increase.
The Italian study examined 245 patients of which 155 had been taking dopamine agonists and 90 were on other medication.
Their results showed that moderate to severe heart valve leaks (i.e. clinically important regurgitation, graded 3 or 4 according to the American Society of Echocardiography system) were found with significantly greater frequency in patients taking pergolide (23.4 per cent increase) and cabergoline (28.6 per cent increase) compared to patients taking non ergot-derived dopamine agonists.
The two studies conclude that the risk of developing clinically important valve regurgitation is significantly greater in patients on pergolide or cabergoline. They suggest this information should form part of the risk versus potential benefit decision when prescribing such drugs in the future.
A dopamine receptor agonist is a drug that behaves like dopamine – it’s a “key” that fits in the same receptor “keyhole” as naturally produced dopamine. (This is different to an antagonist drug which has a blocking effect on the receptors).
Dopamine-receptors play an important role in the brain’s ability to learn and control movement. They are special proteins that lie between the inner and outer layer of the membrane around brain and other nerve cells. There are five types of dopamine receptors, each type playing a different role in controlling the response of the cell to the arrival of a dopamine neurotransmitter molecule (also known as a dopamine ligand since it binds to the receptor in order to act on the cell).
Dopamine is both a hormone and a neurotransmitter. When the delicate balance between production and destruction of dopamine, its inhibition and excitation, and the various connections between the different types of receptors is upset, different conditions emerge. One of these is Parkinson’s disease, associated with low levels of dopamine. Too little dopamine reduces the ability of the brain and nervous system to smoothly perform motor functions, leading to the jerky movements in people who have the disease.
Dopamine is a natural chemical produced in the brain. It does not cross the blood brain barrier, so taking a dose of dopamine would have no effect on the brain. That is why drugs such as dopamine receptor agonists and antagonists are used to control the action of dopamine. However, because dopamine has a number of roles, for instance it is also a hormone, drugs that behave like it will also “interfere” in these other processes.
In the case of these two studies it is thought that the drugs interfered with the function of a receptor known as 5-HT2B, which can seriously impair the function of a heart valve, sometimes fatally.
Ergot-derived means that the drugs are produced using a fungus commonly known as ergot, which is parasitic on grains and grasses such as rye. Many pharmaceuticals are made from it. For instance the hallucinatory drug LSD was first made from ergot.
Ergot is the French for sprocket, describing the toothed shape of the fungal sclerotic growth that gradually replaces the ripening grains of the infected plant. People consuming ergot at the wrong stage of the fungus life cycle deveop ergotism the symptoms of which vary (convulsions, gangrene) depending on the species of fungus. Outbreaks of ergotism were common in Europe in medieval times and even before that, especially among poor rural communities where the staple diet was rye and the climate mainly wet and cool, ideal conditions for the fungus.
“Dopamine Agonists and the Risk of Cardiac-Valve Regurgitation.”
René Schade, M.D., Frank Andersohn, M.D., Samy Suissa, Ph.D., Wilhelm Haverkamp, M.D., Ph.D., and Edeltraut Garbe, M.D., Ph.D.
NEJM Volume 356:29-38, January 4, 2007, Number 1.
“Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease”
Renzo Zanettini, M.D., Angelo Antonini, M.D., Gemma Gatto, M.D., Rosa Gentile, M.D., Silvana Tesei, M.D., and Gianni Pezzoli, M.D.
NEJM Volume 356:39-46, January 4, 2007, Number 1.
Written by: Catharine Paddock
Writer: Medical News Today