Pleuropulmonary Fibrosis After Long-term Treatment With the Dopamine Agonist Pergolide for Parkinson Disease

Tintner, Ron; Manian, Prasad; Gauthier, Polly; Jankovic, Joseph

doi:10.1001/archneur.62.8.1290

Cited by 55 publications

(21 citation statements)

References 37 publications

(15 reference statements)

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“…In contrast to most ergoline derivatives including ergotamine, pergoline, cabergoline and bromocriptine, terguride is a potent 5HTR 2A and 5HTR 2B receptor antagonist 24. Chronic treatment with ergoline derivatives such as pergolide and, to a lesser extent, cabergoline or with anorexic drugs such as fenfluramine has been associated with retroperitoneal, pleural and pericardial fibrosis as well as valvular heart disease 42 43. These drugs exhibit 5-HTR 2B receptor agonist properties.…”

Section: Discussionmentioning

confidence: 99%

Increased expression of 5-hydroxytryptamine2A/B receptors in idiopathic pulmonary fibrosis: a rationale for therapeutic intervention

Königshoff

Dumitrascu

Udalov

et al. 2010

Thorax

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Background Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and limited responsiveness to available treatments. It is characterised by epithelial cell injury, fibroblast activation and proliferation and extracellular matrix deposition. Serotonin (5-hydroxytryptamine; 5-HT) induces fibroblast proliferation via the 5-HTR 2A and 5-HTR 2B receptors, but its pathophysiological role in IPF remains unclear. A study was undertaken to determine the expression of 5-HT receptors in IPF and experimental lung fibrosis and to investigate the effects of therapeutic inhibition of 5-HTR 2A/B signalling on lung fibrosis in vivo and in vitro.Methods and results Quantitative RT-PCR showed that the expression of 5-HTR 1A/B and 5-HTR 2B was significantly increased in the lungs of patients with IPF (n¼12) and in those with non-specific interstitial pneumonia (NSIP, n¼6) compared with transplant donors (n¼12). The expression of 5-HTR 2A was increased specifically in IPF lungs but not in NSIP lungs. While 5-HTR 2A protein largely localised to fibroblasts, 5-HTR 2B localised to the epithelium. To assess the effects of 5HTR 2A/B inhibition on fibrogenesis in vivo, mice were subjected to bleomycin-induced lung fibrosis and treated with the 5-HTR 2A/B antagonist terguride (or vehicle) in a therapeutic approach (days 14e28 after bleomycin). Terguride-treated mice had significantly improved lung function and histology and decreased collagen content compared with vehicle-treated mice. Functional in vitro studies showed that terguride is a potent inhibitor of transforming growth factor b 1 -or WNT3a-induced collagen production. Conclusion The studies revealed an increased expression of 5-HTR 2A specifically in IPF. Blockade of 5-HTR 2A/B signalling by terguride reversed lung fibrosis and is thus a promising therapeutic approach for IPF.

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Section: Discussionmentioning

confidence: 99%

Increased expression of 5-hydroxytryptamine2A/B receptors in idiopathic pulmonary fibrosis: a rationale for therapeutic intervention

Königshoff

Dumitrascu

Udalov

et al. 2010

Thorax

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“…Used in doses of 2.5-10 mg daily (bromocriptine) and 0.25-2 mg weekly (cabergoline), long-term adverse effects have not been reported in patients with prolactinomas. In contrast, pleural thickening, parenchymal lung disease, and serosal fibrosis have been reported in patients with Parkinson's disease receiving chronic therapy with bromocriptine, cabergoline, and pergolide (42,43).…”

Section: Safety Of Dopamine Agonistsmentioning

confidence: 96%

Long-Term Management of Prolactinomas

Schlechte

2007

The Journal of Clinical Endocrinology &Amp; Metabolism

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Prolactinomas are a frequent cause of gonadal dysfunction and infertility, especially in young women. The regulation of prolactin secretion and the efficacy of dopamine agonists in the therapy of prolactinomas are well established. The current challenges in management of prolactinomas are related to follow-up after successful therapy. Issues and questions to be addressed in this approach to long-term management of prolactinomas include the frequency of radiographic monitoring, effect of pregnancy and menopause, safety of estrogen in women taking oral contraceptives, and the potential for discontinuation of dopamine agonist therapy.

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“…On the other hand, because retroperitoneal, pericardial, and pleuropulmonary fibrosis have been associated with the use of ergot derivatives (Rinne, 1987;Tintner et al, 2005), the use of this specific group of dopamine-related drugs as treatment for PD was ended, and pergolide in particular was removed from the market.…”

Section: Dopamine Replacement Therapymentioning

confidence: 99%

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Smith

Wichmann

Factor

et al. 2011

Neuropsychopharmacol

194

137

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The demonstration that dopamine loss is the key pathological feature of Parkinson's disease (PD), and the subsequent introduction of levodopa have revolutionalized the field of PD therapeutics. This review will discuss the significant progress that has been made in the development of new pharmacological and surgical tools to treat PD motor symptoms since this major breakthrough in the 1960s. However, we will also highlight some of the challenges the field of PD therapeutics has been struggling with during the past decades. The lack of neuroprotective therapies and the limited treatment strategies for the nonmotor symptoms of the disease (ie, cognitive impairments, autonomic dysfunctions, psychiatric disorders, etc.) are among the most pressing issues to be addressed in the years to come. It appears that the combination of early PD nonmotor symptoms with imaging of the nigrostriatal dopaminergic system offers a promising path toward the identification of PD biomarkers, which, once characterized, will set the stage for efficient use of neuroprotective agents that could slow down and alter the course of the disease.

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Pleuropulmonary Fibrosis After Long-term Treatment With the Dopamine Agonist Pergolide for Parkinson Disease

Cited by 55 publications

References 37 publications

Increased expression of 5-hydroxytryptamine2A/B receptors in idiopathic pulmonary fibrosis: a rationale for therapeutic intervention

Increased expression of 5-hydroxytryptamine2A/B receptors in idiopathic pulmonary fibrosis: a rationale for therapeutic intervention

Long-Term Management of Prolactinomas

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

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