title: Bifunctional agents for reperfusion arrhythmias: novel hybrid vitamin E/class I antiarrhythmics.
abstract: We have synthesized a series of hybrid compounds combining the pharmacophoric redox moieties of vitamin E and key features responsible for the antiarrhythmic properties of the class I antiarrhythmics procainamide and lidocaine. Procainamide analogue (2a) and lidocaine analogues (14a) and (14b) are very strong inhibitors of lipid peroxidation. All analogues tested at 100 or 30 microM enhanced the post ischemic recovery without inducing ventricular fibrillations while there was no evidence in our experiments for drug-induced pro-arrhythmia. In addition, they induced a widening of the QRS intervals. Our data suggest that the efficacy of the new compounds in preventing reperfusion arrhythmias could be attributed to their combined effects involving inhibition of free radical mediated damage coupled with antiarrhythmic properties.
authors: Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vassileos Constantinou Ave., 116 35, Athens, Greece. mkoufa@eie.gr
authors: Maria
authors: M
authors: Koufaki
authors: Theodora
authors: T
authors: Calogeropoulou
authors: Eleni
authors: E
authors: Rekka
authors: Michael
authors: M
authors: Chryselis
authors: Panagiota
authors: P
authors: Papazafiri
authors: Catherine
authors: C
authors: Gaitanaki
authors: Alexandros
authors: A
authors: Makriyannis
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008012:Lidocaine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation; D009682:Magnetic Resonance Spectroscopy; D011342:Procainamide / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015424:Reperfusion; D014810:Vitamin E / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D014810:Vitamin E; D008012:Lidocaine; D011342:Procainamide