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The Discovery of 5-HT2B Receptor Pharmacology Through the Understanding of Drug-Induced Valvulopathy

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5-HT2B Receptors

Part of the book series: The Receptors ((REC,volume 35))

Abstract

Chronic valvular heart disease (VHD) with myxomatous degeneration and thickening of the mitral valve leaflets is a deleterious side effect of many drugs targeting the serotonergic system. It is due to the poor selectivity of these old drugs and thus stimulation of 5-HT2 receptors as off targets by either the main compound or their metabolites. Consequently, many drugs are now withdrawn from the market due to VHD development, and because binding of 5-HT2B receptor refers to as a “black box warning”. However, 5-HT2 receptors are involved in many pathological conditions and represent promising targets for the development of new drugs. Thus, a better understanding of the pharmacology of 5-HT2 receptors, more specifically of 5-HT2B receptor, could help design new drugs devoid of cardiac side effects. We review here cellular mechanisms involved in valvular degeneration and regulated by serotonin stimulation, as well as the pharmacology of 5-HT2B receptor agonists that could provide new insight into VHD development.

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Authors and Affiliations

  1. Laboratoire de Pharmacologie et Toxicologie NeuroCardiovasculaire, Strasbourg, France

    Alizée Arnoux & Estelle Ayme-Dietrich

  2. Mécanismes centraux et périphériques de la Neurodégénerescence, Strasbourg, France

    Alizée Arnoux

  3. Domain Therapeutics, Illkirch-Graffenstaden, France

    Alizée Arnoux

  4. Département Universitaire de Pharmacologie, Addictologie, Toxicologie et Thérapeutique, Faculté de Médecine Maïeutiqueet Sciences de la santé, Strasbourg, France

    Estelle Ayme-Dietrich

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  1. Alizée Arnoux
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Correspondence to Estelle Ayme-Dietrich .

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Editors and Affiliations

  1. Inserm, U1270, Institut du Fer a Moulin, Paris, France

    Luc Maroteaux

  2. Pharmacology, Strasbourg Medical school, Strasbourg, France

    Laurent Monassier

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Arnoux, A., Ayme-Dietrich, E. (2021). The Discovery of 5-HT2B Receptor Pharmacology Through the Understanding of Drug-Induced Valvulopathy. In: Maroteaux, L., Monassier, L. (eds) 5-HT2B Receptors. The Receptors, vol 35. Springer, Cham. https://doi.org/10.1007/978-3-030-55920-5_12

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