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 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.
Kennedy
J A
JA
Department of Clinical Chemistry, Queen Elizabeth Hospital, University of Adelaide, Woodville South, South Australia. jkennedy@tqehsmtp.tqeh.sa.gov.au
Horowitz
J D
JD
D000638:Amiodarone / Q000494:pharmacology; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D017202:Myocardial Ischemia / Q000188:drug therapy; D009206:Myocardium / Q000201:enzymology* / Q000648:ultrastructure; D010480:Perhexiline / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014292:Trimetazidine / Q000494:pharmacology*
D002334:Carnitine O-Palmitoyltransferase; D010480:Perhexiline; D000638:Amiodarone; D014292:Trimetazidine