Comparative electropharmacology of mexiletine, lidocaine and quinidine in a canine Purkinje fiber model.
Although said to be lidocaine-like, there is evidence that mexiletine has some properties similar to those of quinidine. To evaluate the relationship between the effects of these three drugs we analyzed their effects on action potentials of Purkinje fibers from canine false tendons. Experiments with each drug were done on single preparations from each of six dogs over the concentration range 0.31 to 10.0 X 10(-5) M. Lidocaine shortened action potential duration and effective refractory period with a log concentration-response relationship. The maximum velocity of phase "0" (Vmax) was unaffected at low concentrations and only slightly depressed at high concentrations. Quinidine also shortened action potential duration and effective refractory period but the effect levelled off at midrange and was reversed at higher concentrations. Quinidine depressed Vmax throughout the concentration range studied. Mexiletine shortened action potential duration with a log concentration response relationship. Effective refractory period was shortened at low concentrations but the effect levelled off and then reversed at higher concentrations of the drug. Mexiletine had no effect on Vmax at the lower end of the concentration curve but did suppress this parameter at higher concentrations. Mexiletine resembled lidocaine in its effect on Vmax and action potential duration whereas the effects of quinidine on these two parameters were distinct. On the other hand, the effects of mexiletine on effective refractory period were more akin to quinidine than lidocaine.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008801:Mexiletine / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology; D011802:Quinidine / Q000494:pharmacology*; D012964:Sodium / Q000502:physiology; D013997:Time Factors
D011437:Propylamines; D008801:Mexiletine; D008012:Lidocaine; D012964:Sodium; D011802:Quinidine