Antiarrhythmic activity in occlusion-reperfusion model of 1-(1H-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino} propan-2-ol and its enantiomers

• Published in: Clinical and experimental pharmacology & physiology 2016-01, Vol.43 (1), p.81-87
• Main Authors: Bednarski, Marek, Otto, Monika, Dudek, Magdalena, Siwek, Agata, Zygmunt, Małgorzata, Knutelska, Joanna, Nowiński, Leszek, Groszek, Grażyna, Sapa, Jacek
• Format: Article
• Language: English
• Subjects: adrenolytic; Animals; Anti-Arrhythmia Agents - chemistry; Anti-Arrhythmia Agents - pharmacology; Anti-Arrhythmia Agents - therapeutic use; antioxidant activity; Antioxidants - metabolism; Arrhythmias, Cardiac - complications; Arrhythmias, Cardiac - prevention & control; Brain - drug effects; Brain - metabolism; Calcium - metabolism; carvedilol; Coronary Occlusion - complications; Disease Models, Animal; Electrocardiography; Heart - drug effects; Heart - physiopathology; Indoles - chemistry; Indoles - pharmacology; Indoles - therapeutic use; Lipid Peroxidation - drug effects; Male; Myocardial Reperfusion Injury - complications; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - physiopathology; Oxidation-Reduction; Propanolamines - chemistry; Propanolamines - pharmacology; Propanolamines - therapeutic use; Rats; Rats, Wistar; reperfusion; Stereoisomerism
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.12491

Summary Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide, especially in developed countries. The most serious problem after myocardial infarction is reperfusion injury that manifests as functional impairment, arrhythmia, and accelerated progression of cell death in certain critically injured myocytes. Subsequently the infarcted myocardium develops features of necrosis and reactive inflammation. To reduce lethal reperfusion injury in patient with AMI antioxidants, anti‐inflammatory agents, adenosine, opioids, metabolic modulators (glucose, insulin, and potassium, nicorandil and agents which reduce intracellular Ca2+ overload and inhibit Na+‐H+ exchange) are used. In this study a novel compound (compound 9) 1‐(1 h‐indol‐4‐yloxy)‐3‐{[2‐(2‐methoxyphenoxy) ethyl]amino}propan‐2‐ol and its enantiomers are examined in arrhythmia associated with coronary artery occlusion and reperfusion in a rat model. Antioxidant properties are also determined for test compounds using the malondialdehyde (MDA) lipid peroxidation and ferric reducing antioxidant power (FRAP) tests. In summary, the tested compounds, especially the S enantiomer has a strong antiarrhythmic activity in a model of occlusion and reperfusion of the left coronary artery which is probably related to their adrenolytic action. In contrast to carvedilol, none of the test compound reduced the lipid peroxidation but increased ferric reducing antioxidant power. In the antioxidant effect, there was no difference between the optical forms of compound 9.