Mitochondria as target for antiischemic drugs.
The cessation of blood flow followed by a reperfusion period results in severe damages to cell structures. This induces a complex cascade of events involving, more particularly, a loss of energy, an alteration of ionic homeostasis promoting H(+) and Ca(2+) build up and the generation of free radicals. In this context, mitochondria are highly vulnerable and play a predominant role in the cell signaling leading from life to death. This is why, recently, efforts to find an effective therapy for ischemia-reperfusion injury have focused on mitochondria. This review summarizes the pharmacological strategies which are currently developed and the potential mitochondrial targets which could be involved in the protection of cells.
Morin
D
D
Laboratoire de Pharmacologie and Centre National de La Recherche Scientifique, Faculté de Médecine de Paris XII, 8 rue du General Sarrail, F-94010 Créteil, France. morin@univ-paris12.fr
Hauet
T
T
Spedding
M
M
Tillement
J
J
D000083:Acetanilides; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D003067:Coenzymes; D016503:Drug Delivery Systems / Q000379:methods*; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006801:Humans; D007473:Ion Channels; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010879:Piperazines / Q000008:administration & dosage; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D000069458:Ranolazine; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000378:metabolism; D014292:Trimetazidine / Q000008:administration & dosage; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives; D014665:Vasodilator Agents / Q000008:administration & dosage
D000083:Acetanilides; D000975:Antioxidants; D003067:Coenzymes; D004791:Enzyme Inhibitors; D007473:Ion Channels; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010879:Piperazines; D015221:Potassium Channels; D019831:Sodium-Calcium Exchanger; D014665:Vasodilator Agents; D014451:Ubiquinone; D000069458:Ranolazine; C024989:coenzyme Q10; D014292:Trimetazidine