Kennedy J A, Horowitz J D
Department of Clinical Chemistry, Queen Elizabeth Hospital, University of Adelaide, Woodville South, South Australia.
Cardiovasc Drugs Ther. 1998 Sep;12(4):359-63. doi: 10.1023/a:1007768716934.
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 mumol/L) or amiodarone (IC50 228 mumol/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.
抗心绞痛药物曲美他嗪抗缺血作用的作用机制尚不清楚。然而，有证据表明它能抑制长链脂肪酸氧化，这可能会提高心肌氧利用效率。我们研究了曲美他嗪（0.1 - 5 mmol/L）对大鼠心肌中肉碱棕榈酰转移酶-1（CPT-1）活性的影响。曲美他嗪抑制CPT-1（IC50为1.3 mmol/L）；这种作用的效力低于哌克昔林（IC50为77 μmol/L）或胺碘酮（IC50为228 μmol/L），但似乎与哌克昔林和胺碘酮在酶的相似位点相互作用。得出的结论是，曲美他嗪作为CPT-1抑制剂的效力相对较低，这使得这一机制不太可能解释其治疗性抗缺血作用。
