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Effect of Trimetazidine on Carnitine Palmitoyltransferase-1 in the Rat Heart

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Abstract

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 (0.1–5mmol/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 μmol/L) or amiodarone (IC50 228 μmol/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.

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Authors and Affiliations

  1. Department of Clinical Chemistry, The Queen Elizabeth Hospital, University of Adelaide, Woodville South, South Australia

    J.A Kennedy

  2. Department of Cardiology, The Queen Elizabeth Hospital, University of Adelaide, Woodville South, South Australia

    J.D Horowitz

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  1. J.A Kennedy
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Kennedy, J., Horowitz, J. Effect of Trimetazidine on Carnitine Palmitoyltransferase-1 in the Rat Heart. Cardiovasc Drugs Ther 12, 359–363 (1998). https://doi.org/10.1023/A:1007768716934

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