From: MitoTox: a comprehensive mitochondrial toxicity database
Indication | Drug Name | Mechanism of mitochondrial toxicity | Status | Toxicity | t1/2 (h)a | Protein binding (%)a | LD50 (rat)a |
---|---|---|---|---|---|---|---|
Antidiabetic | Troglitazone | Inhibition of ETC | Withdrawn, 2000 | Hepatotoxicity | 16–34 | > 99% | 1.9768 mol/kg |
Rosiglitazone | Inhibition of ETC | Approved, investigational | Cardiotoxicity | 3–4 | 99.8% | 2.4515 mol/kg | |
Pioglitazone | Inhibition of ETC | Approved, investigational | Cardiotoxicity | 3–7/16–24 | > 99% | 2.0115 mol/kg | |
Ciglitazone | Inhibition of ETC | Discontinued | NA | NA | NA | NA | |
Darglitazone | Inhibition of ETC | Discontinued | NA | NA | NA | NA | |
Muraglitazar | Inhibition of ETC | Discontinued | NA | NA | NA | NA | |
Metformin | Inhibition of complex I; uncoupling; impaired TCA cycle | Approved | Lactic acidosis | 6.2 | > 90% | 1000 mg/kg | |
Anticancer | Doxorubicin | Increased ROS; mtDNA adduct; iron overload | Approved | Cardiotoxicity | 20–48 | 74–76% | 21.8 mg/kg |
Cisplatin | Inhibition of Complex I | Approved | Nephrotoxicity | 0.3–0.7 | > 90% | 2.7612 mol/kg | |
Hyperlipidemia | Fenofibrate | Inhibition of complex I | Approved | Hepatotoxicity | 20 | ~ 99% | > 2000 mg/kg |
Clofibrate | Inhibition of complex I | Approved | Hepatotoxicity | 18–22 | 95–97% | 940 mg/kg | |
Ciprofibrate | Inhibition of complex I | Approved | Hepatotoxicity | NA | NA | NA | |
Psychotropic | Valproic acid | Inhibition of TCA cycle | Approved | Coma and respiratory depression | 9–16 | 90% | 670 mg/kg |
Clozapine | Inhibition of the ETC | Approved | Metabolic syndrome | 8 | 97% | 3.0838 mol/kg | |
Fluoxetine | Uncoupler | Approved | CNS, GI effects | 1–3 days | 94.5% | 2.6048 mol/kg | |
Nefazodone | Inhibition of Complex I and complex IV | Withdrawn | Hepatotoxicity | 2–4 | > 99% | 2.9067 mol/kg | |
Analgesic | Acetaminophen | Oxidative stress | Approved | Hepatotoxicity | 1–4 | 25% | 1944 mg/kg |
Aspirin | mPTP potentiation | Approved | Cardiotoxicity, GI effects | 0.25 | 99.5% | 920–1480 mg/kg | |
Diclofenac | Inhibition of ETC and ATP synthase | Approved | Nephrotoxicity | 2 | > 99% | 3.6447 mol/kg | |
Antibacterial | Imipenem | Oxidative stress | Approved | Nephrotoxicity | 1.3–5.1 | 20% | 1.8089 mol/kg |
Chloramphenicol | Depletion of iron | Approved | Aplastic anemia | 1.5–3.5 | 50–60% | 2500 mg/kg | |
Antiviral | Zidovudine | mtDNA replication (inhibit mtDNA polymerase-γ) | Approved | Myopathy | 0.5–2.9 | 30–38% | NA |