Publication details

Molekulární podstata vzniku nežádoucích účinků haloperidolu

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Title in English Molecular mechanisms of adverse side effects of haloperidol
Authors

RAUDENSKÁ Martina GUMULEC Jaromír SZTALMACHOVÁ Markéta NOVÁKOVÁ Marie KIZEK René MASAŘÍK Michal

Year of publication 2013
Type Article in Periodical
Magazine / Source Česká a slovenská psychiatrie
MU Faculty or unit

Faculty of Medicine

Citation
web http://www.cspsychiatr.cz/dwnld/CSP_2013_6_298_303.pdf
Field Physiology
Keywords haloperidol; oxidative stress; cardiotoxicity; antipsychotic drug; molecular mechanisms
Description Haloperidol (HP) is the most potent neuroleptic agent which has been widely used not only in psychiatric patients but also in patients with other diagnoses, mainly geriatric and surgical, for the control of severe agitation, e.g. after general anaesthesia. Haloperidol was considered to be a safe drug, but unfortunately its therapeutic effects also come with severe extrapyramidal side effects, resulting in movement disorders, tardive dyskinesia, prolonging of the corrected QT interval which can cause severe arrhythmias such as Torsade de Pointes (TdP) and eventually result in sudden cardiac death. Large interindividual differences in the incidence of side effects have been demonstrated. The possible mechanism of HP cytotoxicity is an effect of oxidative stress, especially peroxidation of membrane lipids. Support for lipid peroxidative damage in patients with movement disorders comes from reports of amelioration of TD after treatment with vitamin E, or other lipid soluble antioxidants. HP is a dopamine antagonist and its major site of action is the dopamine D2 receptor (DRD2), which exhibits high affinity for the drug. It was found that HP affects not only DRD2 signalisation, but also the expression of DRD2 and other genes.
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