[Medicines interacting with mitochondria: anti-ischemic effects of trimetazidine].
While mitochondria are key factors in energy production in cells they are also key factors in their life cycle because under certain circumstances they can provoke cellular apoptosis. Some 45 per cent of myocardial volume is taken up by mitochondria. Furthermore, mitochondria are key to many aspects of neuronal activity and can trigger neurodegenerative processes. Lipid oxidation is responsible for the production of much ATP resynthesis in the heart but this process is less oxygen efficient than glucose oxidation. During ischaemia, lipid oxidation is suddenly blocked, but markedly increased during reperfusion, causing accumulation of potentially toxic metabolites (acylcarnitines, acyl-CoA, lysophospholipids). These metabolites can change calcium handling, inducing arrhythmias. Trimetazidine, and another product in development, ranolazine, by inhibiting lipid oxidation favours glucose oxidation and inhibits the production of deleterious lipid metabolites. Thus this class of drugs can have beneficial effects on myocardial metabolism without direct haemodynamic effects.
Spedding
M
M
Institut de Recherches Internationales Servier (I.R.I.S.), Neuilly sur Seine, France.
Tillement
J P
JP
Morin
D
D
Le Ridant
A
A
D000083:Acetanilides; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D020169:Caspases / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006801:Humans; D007511:Ischemia / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D008929:Mitochondria, Heart / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D000069458:Ranolazine; D015427:Reperfusion Injury / Q000517:prevention & control; D013831:Thiamine / Q000031:analogs & derivatives / Q000494:pharmacology; D014292:Trimetazidine / Q000494:pharmacology*
D000083:Acetanilides; D004272:DNA, Mitochondrial; D004791:Enzyme Inhibitors; D010879:Piperazines; C031331:sulbutiamine; D000255:Adenosine Triphosphate; D000069458:Ranolazine; D002334:Carnitine O-Palmitoyltransferase; D020169:Caspases; D014292:Trimetazidine; D013831:Thiamine