Lubeluzole-induced prolongation of cardiac action potential in rabbit Purkinje fibres.
Lubeluzole, a novel neuroprotective compound, has been associated with cases of QT interval prolongation but its effects on the cardiac action potential have not been described to date. Thus, the electrophysiological effects of lubeluzole were studied in rabbit isolated Purkinje fibres. The results demonstrate that lubeluzole (0.001-1 microM) concentration-dependently lengthened action potential duration at 50% and 90% of repolarization (APD50 and APD90) without significantly modifying other parameters. Furthermore, APD lengthening induced by lubeluzole was not significantly decreased by reducing the basic cycle length (from 3,000 to 1,000 ms). The results demonstrate that lubeluzole potently and concentration-dependently increases APD from 0.01 microM, consistent with class III-type antiarrhythmic actions, which is likely to underlie QT interval prolongation induced by the drug.
Le Grand
B
B
Centre de recherche Pierre Fabre, division of cardiovascular diseases, Castres, France.
Dordain-Maffre
M
M
John
G W
GW
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D013844:Thiazoles / Q000494:pharmacology*
D002317:Cardiovascular Agents; D010880:Piperidines; D013844:Thiazoles; C097722:lubeluzole