Title:Haloperidol Cytotoxicity and Its Relation to Oxidative Stress
Volume: 13
Issue: 14
Author(s): Martina Raudenska, Jaromir Gumulec, Petr Babula, Tibor Stracina, Marketa Sztalmachova, Hana Polanska, Vojtech Adam, Rene Kizek, Marie Novakova and Michal Masarik
Affiliation:
Keywords:
Arrhytmia, cardiotoxicity, dopamine, haloperidol, oxidative stress, Torsade de Pointes.
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.
