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pubmed:abstractText |
The Na+ channel blocking activity and the antiarrhythmic effects of riluzole, and established anticonvulsants (lamotrigine and lifarizine) and class I antiarrhythmics (lidocaine, flecainide and disopyramide) were studied under in vitro and in vivo conditions. Guinea-pig cardiac Purkinje fibres were superfused with Tyrode solution and electrically driven for recording action potentials with intracellular microelectrodes. In these preparations paced at 1 Hz, all compounds tested produced concentration-dependent (0.3-100 microM) reductions in the maximum rate of depolarization of the action potential (Vmax). For riluzole, phenytoin and carbamazepine this effect was frequency-independent (0.5-6 Hz) but for lamotrigine, lifarizine, lidocaine, flecainide and disopyramide it was frequency-dependent. In anaesthetized rats, riluzole, in contrast to flecainide, did not delay the appearance of aconitine-induced arrhythmias. Riluzole (0.3-3.9 mg/kg, i.v.) also lacked notable cardiac electrophysiological effects in anaesthetized dogs. At an i.v. dose of 3.0 mg/kg riluzole failed to restore a normal sinus rhythm in conscious dogs with polymorphic arrhythmias produced by ligation of the left anterior descending coronary artery 24 h earlier. These results indicate that riluzole, phenytoin and carbamazepine, unlike lamotrigine, lifarizine and flecainide, block cardiac Na+ channels in a frequency-independent manner. This property may account for the lack of antiarrhythmic activity of riluzole, phenytoin and carbamazepine in animal models of arrhythmias that respond to class I antiarrhythmic drugs. It may also account for the clinical observation that riluzole does not seem to cause the unfavourable electrocardiographic changes characteristic of drugs that block cardiac Na+ channels in a frequency-dependent manner.
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