Comparison in vitro of the electrophysiological effects of lorcainide and its metabolite norlorcainide.
The effects of lorcainide and its metabolite norlorcainide on the maximal rate of depolarization (Vmax) were compared at different rates of stimulation and at various membrane potentials in ventricular muscle preparations of guinea-pig heart. A standard microelectrode technique was used. The results show that lorcainide and norlorcainide exerted qualitatively similar effects; they both depressed Vmax in a frequency- and potential-dependent way. The following quantitative differences were found: lorcainide was about 50% more potent in depressing Vmax; this difference in potency was observed at 1 and 2 Hz stimulation rates; the block by lorcainide was clearly potential-dependent; in the case of norlorcainide this effect was weak; the onset and removal of block were about twice as fast with lorcainide; the block per action potential was greater with lorcainide. The electrophysiological effects were decreased in the presence of alpha 1-acid glycoprotein, though to a similar extent with both drugs. Taking into account the difference in potency found in the present experiments and the difference in plasma concentration described in the literature, it is concluded that the parent drug and its metabolite both contribute to about the same extent to the in vivo effect of oral treatment with lorcainide.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D044482:Benzeneacetamides; D001798:Blood Proteins / Q000378:metabolism; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding
D000889:Anti-Arrhythmia Agents; D044482:Benzeneacetamides; D001798:Blood Proteins; D010880:Piperidines; C031145:norlorcainide; C015970:lorcainide