Effects of Lidocaine and Its Metabolite. Monoethylglycine Xylidide (MEGX ) on Maximum Rate of Rise (Vmax) of Action Potential Upstroke in Guinea-pig Papillary Muscles

We studied the effects of lidocaine and its metabolite, MEGX, on the sodium current, using maximum rate of rise of action potential (Vmax) as an indicator, in isolated guinea-pig papillary muscles. Both lidocaine and MEGX produced dose (5,10,20μg･ml^<-1> )- and rate (2,3,4Hz) - dependent depression of Vmax without significant changes in resting membrane potentials at an extracellular potassium concentration ([K]o) 5.4mmol･1^<-1>. Both drugs shortened the action potential duration. The recovery kinetics of Vmax was studied by either applying premature stimuli at the basic driving rate of 0.25Hz or by stopping the basic driving of 1Hz for Is to 60s. A slow component (time constant : 176~206ms for lidocaine,300~340ms for MEGX) was observed in premature response, and a slower component (time constant:3~4s for MEGX) was observed in the first response after stopping stimulation. At 10mmol･1＾<-1>[K]o, both lidocaine(10μg･ml^<-1>) and MEGX(10μg･ml^<-1>) further decreased the Vmax at the steady-state stimulation of 1Hz, and they caused a significant rate-dependent decrease in Vmax and slowed the recovery kinetics of Vmax. These results suggest that MEGX has rate- and voltage-dependent blocking effects on Vmax as lidocaine and that the actions of lidocaine may be potentiated or prolonged in the patients with elevated plasma MEGX concentration.

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lidocaine moneoethylyglycine xylidide (meGX)