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Investigation of class I anti-arrhythmic drug actions on guinea-pig cardiac mitochondrial lactate dehydrogenase activity.

Abstract：

:1. The effects of the Class I anti-arrhythmic drugs quinidine, procainamide, lidocaine, phenytoin and tocainide on mitochondrial lactate dehydrogenase 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. Lidocaine 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 mmol/L and tocainide 2.7 +/- 0.3 mmol/L and 44.6 +/- 2.5 mmol/L. 3. According to the IC50 values, this is the order of their inhibitory potencies: phenytoin > quinidine > lidocaine > tocainide > procainamide. This trend is in general agreement with the lipophilicity rank of the drugs. 4. It is concluded, therefore, that inhibition of mitochondrial lactate dehydrogenase is a property shared by most Class I anti-arrhythmic drugs which may depend on their lipophilicity and possibly their membrane stabilizing effects.

journal_name

Clin Exp Pharmacol Physiol

journal_title

Clinical and experimental pharmacology & physiology

authors

Dzimiri N,Almotrefi AA

doi

10.1111/j.1440-1681.1993.tb01671.x

subject

Has Abstract

pub_date

1993-04-01 00:00:00

pages

201-6

issue

4

eissn

0305-1870

issn

1440-1681

journal_volume

20

pub_type

杂志文章

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