Effect of trimetazidine on carnitine palmitoyltransferase-1 in the rat heart

The mechanism of action of the antiischemic effect of the antianginal agent trimetazidine remains uncertain. However, there is evidence that it inhibits long-chain fatty acid oxidation, which may increase the efficiency of myocardial oxygen utilization. We examined the effects of trimetazidine (0.1-5 mmol/L) on the activity of carnitine palmitoyltransferase-1 (CPT-1) in rat myocardium. Trimetazidine inhibited CPT-1 (IC50 1.3 mmol/L); this effect was less potent than that of perhexiline (IC50 77 mu mol/L) or amiodarone (IC50 228 mu mol/L), but appeared to interact with the enzyme at a similar site as that of both perhexiline and amiodarone. It is concluded that the relatively low potency of trimetazidine as a CPT-1 inhibitor makes this an unlikely mechanism to explain its therapeutic antiischemic effect.