Author: Alessandro Cosenzi

Source: Current Pharmaceutical Analysis, Volume 1, Number 1, January 2005 , pp. 93-108(16)

Publisher: Bentham Science Publishers

Abstract:

In 1988 Yanagisawa described endothelins, a new class of vasoconstrictor agents produced by endothelial cells. Further biological effects of these peptides have subsequently been demonstrated, for example, induction of cell proliferation and fibrosis. Two types of endothelin receptors have been described: ET are responsible for endothelininduced vasoconstriction whereas ET induce endothelial cells to release nitric oxide (NO) and prostacyclin. Many antagonists of endothelin receptors have been synthesized and evaluated in animal models and in humans. Satisfactory results have been obtained in animal models of arterial hypertension, pulmonary hypertension, stroke and heart failure but clinical trials have failed to demonstrate that these drugs have a beneficial effect in the treatment of heart failure and a dose-dependent reversible hepatic toxicity has been observed. However, the efficacy of bosentan, a mixed antagonist of endothelin receptors, in the treatment of primary pulmonary hypertension has been demonstrated and the drug is now marketed worldwide for this condition. Further studies are ongoing to evaluate other clinical applications of these drugs. Recently it has been reported that atrasentan, a selective ET antagonist, delayed the progression of hormone-refractory prostate cancer in humans. This review describes the results of the studies performed in animals and in humans and their potential future clinical applications.

Keywords: endothelins; lung; heart; kidney; brain; liver; cancer

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1573412052953337

Affiliations: 1: Dipartimento di Medicina Clinica e Neurologia, University of Trieste, c/o Ospedale di Cattinara, Strada di Fiume 447, 34100 Trieste, Italy.

Publication date: 2005-01-01

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• Current Pharmaceutical Analysis publishes authoritative reviews, written by experts in the field on all the most recent advances in pharmaceutical and biomedical analysis. All aspects of the field are represented including drug analysis, analytical methodology and instrumentation. The journal is essential to all involved in pharmaceutical, biochemical and clinical analysis.

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