title: Haloperidol cytotoxicity and its relation to oxidative stress.
abstract: Haloperidol (HP) is used for the symptomatic treatment of psychosis, manic phases, hyperactivity, aggressiveness, and acute delirium. Long-term use leads to various adverse side effects, especially to severe impairment of extrapyramidal nerve tracts and in particular, altered QT interval and increased incidence of arrhytmias. It is believed that cytotoxicity of HP and its metabolites is responsible for both neurotoxicity and cardiotoxicity. Extrapyramidal and cardiac adverse side effects may be explained by the HP-induced oxidative stress, as implicated by many studies. HP was reported to induce lipid peroxidation with subsequent membrane changes, responsible for cell death. Vice versa, cells resistant to oxidative stress are also resistant to the toxic effects of HP. Similarly, high percentage of patients suffering from extrapyramidal symptoms treated by vitamin E and other lipid-soluble antioxidants demonstrates diminishing of these adverse side effects. HP's ability to induce oxidative stress by multi-modal action (increased metabolism of dopamine, decrease of glutathione content, induction of NF-κB transcription factor, and inhibition of complex I of respiratory chain) has been established just recently. This review brings summarizing view on the cytotoxicity of haloperidol and involvement of reactive oxygen species and oxidative stress HP-induced cytotoxicity.
authors.forename: Martina
authors.initials: M
authors.lastname: Raudenska
authors.forename: Jaromir
authors.initials: J
authors.lastname: Gumulec
authors.forename: Petr
authors.initials: P
authors.lastname: Babula
authors.forename: Tibor
authors.initials: T
authors.lastname: Stracina
authors.forename: Marketa
authors.initials: M
authors.lastname: Sztalmachova
authors.forename: Hana
authors.initials: H
authors.lastname: Polanska
authors.forename: Vojtech
authors.initials: V
authors.lastname: Adam
authors.forename: Rene
authors.initials: R
authors.lastname: Kizek
authors.forename: Marie
authors.initials: M
authors.lastname: Novakova
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic. masarik@med.muni.cz.
authors.forename: Michal
authors.initials: M
authors.lastname: Masarik
mesh_terms: D014150:Antipsychotic Agents / Q000378:metabolism* / Q000627:therapeutic use / Q000633:toxicity; D003693:Delirium / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000378:metabolism* / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D020929:Mitogen-Activated Protein Kinase Kinases; D006220:Haloperidol