T. Yamashita et al., ATTENUATION OF ANTIFIBRILLATORY EFFECTS OF LIDOCAINE BY ITS METABOLITE, GLYCYLXYLIDIDE - APPLICATION OF MODULATED RECEPTOR HYPOTHESIS, Journal of cardiovascular pharmacology, 24(6), 1994, pp. 900-905
Lidocaine, one of the drugs effective in treating ventricular arrhythm
ias in acute myocardial infarction (AMI), sometimes loses its efficacy
after prolonged administration, possibly owing to the counteraction o
f glycylxylidide, one of the metabolites of lidocaine, through modulat
ion of binding of lidocaine to sodium channels. To determine whether g
lycylxylidide interferes with the antiarrhythmic action of lidocaine,
we compared the antifibrillatory effects of lidocaine, glycylxylidide,
and their combination in 14 anesthetized open-chest dogs. Although gl
ycylxylidide alone prolonged intraventricular conduction time (CT) and
did not affect ventricular effective refractory period (VERP), it had
different effects when added to lidocaine; i.e., it had no effect on
intraventricular conduction time but shortened VERP. Although glycylxy
lidide alone did not change ventricular fibrillation threshold (VFT),
the increase in VFT induced by lidocaine was decreased by addition of
glycylxylidide, possibly as a result of competition for the same cardi
ac sodium channels between lidocaine and glycylxylidide with similar o
nset but different offset kinetics, which may explain, at least in par
t, the drug-resistance phenomena that ensue from prolonged lidocaine a
dministration.