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Selegiline is not the only antiparkinsonian drug which has been the
focus of controversy on grounds of safety in the last few years [1].
Dopamine agonists, in particular the dopamine agonists pergolide and
bromocriptine [2], have been reported to be associated with valvulopathy.
This had already been reported with long-term use of other ergot
derivatives such as methysergide and with serotonergic anorectic drugs
such as fenfluramine [3].Van Camp studied 78 parkinsonian patients taking
pergolide and concluded that 33% of them had restrictive valvular changes
on echocardiographic criteria:7% of the group stopped the drug because the
valve disease led to symptoms. The fibrotic valvular changes seen with
pergolide are consistent with the pericardial, pleural and retroperitoneal
fibrosis reported previously with ergot derivatives [4]. A plausible
mechanism for the fibrosis may be the activation of 5-HT2B receptors on
interstitial fibroblasts in each organ [5]. Many issues are still to be
addressed, in particular the true incidence of this side-effect, the risk
factors, which appear to include the total degree of exposure to the drugs
but are also likely to include pharmacogenomic considerations, and the
potential reversibility of the lesions. However, it is important that
clinicians are aware of this potential risk with dopaminergic ergot
derivatives when considering therapeutic strategies in Parkinson's
disease.
1. Ivens NJ, Stowe RL, Marro J et al. Monoamine oxidase type B
inhibitors in early Parkinson's disease: meta-analysis of 17 randomised
trials involving 3525 patients.
BMJ 2004; 329: 593
2. van Camp G, Flamez A, Cosyns B et al. Treatment of Parknsons's disease
with pergolide and relation to restrictive valvular heart disease. Lancet
2004; 363:1179-1183
3. Connolly HM, Crary JL, McGoon MD et al. Valvular heart disease
associated with fenfluramine-phentermine. N Engl J Med 1997;337: 581-588
4.Shaunak S, Wilkins A, Pilling JB, Dick DJ.Pericardial, retroperitoneal,
and pleural fibrosis induced by pergolide.
J Neurol Neurosurg Psychiatry 1999;66:79-81
5.Fitzgerald LW, Burn TC, Brown BS et al, Possible role of vascular
serotonin 5-HT2B receptors in the cardiopathy associated with
fenfluramine. Mol Pharmacol 2000; 57: 75-81
Competing interests:
Each author has given a talk at clinical meetings sponsored by GSK
Competing interests:
No competing interests
06 October 2004
Marie-Helene Marion
Consultant Neurologist and Hon Senior Lecturer
Michael Schachter
St. George's Healthcare NHS Trust,Blackshaw Road,London,SW17 0QT
Safety issues with dopamine agonists
Selegiline is not the only antiparkinsonian drug which has been the
focus of controversy on grounds of safety in the last few years [1].
Dopamine agonists, in particular the dopamine agonists pergolide and
bromocriptine [2], have been reported to be associated with valvulopathy.
This had already been reported with long-term use of other ergot
derivatives such as methysergide and with serotonergic anorectic drugs
such as fenfluramine [3].Van Camp studied 78 parkinsonian patients taking
pergolide and concluded that 33% of them had restrictive valvular changes
on echocardiographic criteria:7% of the group stopped the drug because the
valve disease led to symptoms. The fibrotic valvular changes seen with
pergolide are consistent with the pericardial, pleural and retroperitoneal
fibrosis reported previously with ergot derivatives [4]. A plausible
mechanism for the fibrosis may be the activation of 5-HT2B receptors on
interstitial fibroblasts in each organ [5]. Many issues are still to be
addressed, in particular the true incidence of this side-effect, the risk
factors, which appear to include the total degree of exposure to the drugs
but are also likely to include pharmacogenomic considerations, and the
potential reversibility of the lesions. However, it is important that
clinicians are aware of this potential risk with dopaminergic ergot
derivatives when considering therapeutic strategies in Parkinson's
disease.
1. Ivens NJ, Stowe RL, Marro J et al. Monoamine oxidase type B
inhibitors in early Parkinson's disease: meta-analysis of 17 randomised
trials involving 3525 patients.
BMJ 2004; 329: 593
2. van Camp G, Flamez A, Cosyns B et al. Treatment of Parknsons's disease
with pergolide and relation to restrictive valvular heart disease. Lancet
2004; 363:1179-1183
3. Connolly HM, Crary JL, McGoon MD et al. Valvular heart disease
associated with fenfluramine-phentermine. N Engl J Med 1997;337: 581-588
4.Shaunak S, Wilkins A, Pilling JB, Dick DJ.Pericardial, retroperitoneal,
and pleural fibrosis induced by pergolide.
J Neurol Neurosurg Psychiatry 1999;66:79-81
5.Fitzgerald LW, Burn TC, Brown BS et al, Possible role of vascular
serotonin 5-HT2B receptors in the cardiopathy associated with
fenfluramine. Mol Pharmacol 2000; 57: 75-81
Competing interests:
Each author has given a talk at clinical meetings sponsored by GSK
Competing interests: No competing interests