title: 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.
authors: Biological and Medical Research Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: N
authors: N
authors: Dzimiri
authors: A A
authors: AA
authors: Almotrefi
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology*
chemical_list: D000889:Anti-Arrhythmia Agents; D007770:L-Lactate Dehydrogenase