N. Dzimiri et Aa. Almotrefi, INVESTIGATION OF CLASS-I ANTIARRHYTHMIC DRUG ACTIONS ON GUINEA-PIG CARDIAC MITOCHONDRIAL LACTATE-DEHYDROGENASE ACTIVITY, Clinical and experimental pharmacology and physiology, 20(4), 1993, pp. 201-206
1. The effects of the Class I anti-arrhythmic drugs quinidine, procain
amide, lidocaine, phenytoin and tocainide on mitochondrial lactate deh
ydrogenase activity were compared in guinea-pig heart preparations. 2.
All the tested drugs inhibited the enzyme activity in a concentration
-dependent fashion, exhibiting varying profiles in their actions. Lido
caine exhibited inhibitory concentration 20% (IC20) and IC50 values of
0.52 +/- 0.02 mmol/L and 25.6 +/- 0.5 mmol/L, procainamide 6.0 +/- 0.
2 mmol/L and 108 +/- 7.2 mmol/L, phenytoin 3.4 +/- 0.06 mumol/L and 0.
34 +/- 0.02 mmol/L, quinidine 39.2 +/- 1.2 mumol/L and 9.8 +/- 0.8 mmo
l/L and tocainide 2.7 +/- 0.3 mmol/L and 44.6 +/- 2.5 mmol/L. 3. Accor
ding to the IC50 values, this is the order of their inhibitory potenci
es: phenytoin > quinidine > lidocaine > tocainide > procainamide. This
trend is in general agreement with the lipophilicity rank of the drug
s. 4. It is concluded, therefore, that inhibition of mitochondrial lac
tate dehydrogenase is a property shared by most Class I anti-arrhythmi
c drugs which may depend on their lipophilicity and possibly their mem
brane stabilizing effects.