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• W2143758022 abstract "Existing anti-arrhythmic therapy is hampered by lack of efficacy and unacceptable side effects. Thus, ventricular tachycardia and fibrillation remains the strongest predictor of in-hospital mortality in patients with myocardial infarction. In atrial fibrillation, rhythm control with conventional ion channel blockers provide no therapeutic benefit relative to rate control. Several lines of research indicate that impaired gap junctional cell-to-cell coupling between neighbouring cardiomyocytes is critical for the development of cardiac re-entry arrhythmias. Rotigaptide is the first drug that has been developed to prevent arrhythmias by re-establishing gap junctional intercellular communication. During conditions with acute cardiac ischaemia, rotigaptide effectively prevents induction of both ventricular and atrial tachyarrhythmia. Moreover, rotigaptide effectively prevents ischaemia reperfusion arrhythmias. At the cellular level, rotigaptide inhibits ischaemia-induced dephosphorylation of Ser297 and Ser368, which is considered important for the gating of connexin43 gap junction channels. No drug-related toxicity has been demonstrated at plasma concentrations 77,000 times above therapeutic concentrations. In rats and dogs, rotigaptide reduces infarct size following myocardial infarction. A series of phase I trials has been completed in which rotigaptide has been administered intravenously to ~200 healthy persons. No drug-related side effects have been demonstrated in healthy human beings. Clinical safety, tolerability and efficacy in patients with heart disease are being evaluated in ongoing clinical trials. Rotigaptide represents a pioneering pharmacological principle with a highly favourable preclinical and clinical safety profile, which makes this molecule a promising drug candidate for the prevention of cardiac arrhythmias." @default.
• W2143758022 created "2016-06-24" @default.
• W2143758022 creator A5028811585 @default.
• W2143758022 creator A5035873550 @default.
• W2143758022 creator A5057135061 @default.
• W2143758022 creator A5082781339 @default.
• W2143758022 date "2007-09-06" @default.
• W2143758022 modified "2023-10-15" @default.
• W2143758022 title "Pharmacological Modulation of Gap Junction Function with the Novel Compound Rotigaptide: A Promising New Principle for Prevention of Arrhythmias" @default.
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