Protein thiol oxidation by haloperidol results in inhibition of mitochondrial complex I in brain regions: comparison with atypical antipsychotics

Balijepalli, Sadguna ; Kenchappa, Rajappa S. ; Boyd, Michael R. ; Ravindranath, Vijayalakshmi (2001) Protein thiol oxidation by haloperidol results in inhibition of mitochondrial complex I in brain regions: comparison with atypical antipsychotics Neurochemistry International, 38 (5). pp. 425-435. ISSN 0197-0186

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Official URL: http://linkinghub.elsevier.com/retrieve/pii/S01970...

Related URL: http://dx.doi.org/10.1016/S0197-0186(00)00108-X

Abstract

Usage of 'typical' but not 'atypical' antipsychotic drugs is associated with severe side effects involving extrapyramidal tract (EPT). Single dose of haloperidol caused selective inhibition of complex I in frontal cortex, striatum and midbrain (41 and 26%, respectively) which was abolished by pretreatment of mice with thiol antioxidants, α-lipoic acid and glutathione isopropyl ester, and reversed, in vitro, by disulfide reductant, dithiothreitol. Prolonged administration of haloperidol to mice resulted in complex I loss in frontal cortex, hippocampus, striatum and midbrain, while chronic dosing with clozapine affected only hippocampus and frontal cortex. Risperidone caused complex I loss in frontal cortex, hippocampus and striatum but not in midbrain from which extrapyramidal tract emanates. Inhibition of the electron transport chain component, complex I by haloperidol is mediated through oxidation of essential thiol groups to disulfides, in vivo. Further, loss of complex I in extrapyramidal brain regions by anti-psychotics correlated with their known propensity to generate side-effects involving extra-pyramidal tract.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Antipsychotic; Haloperidol; Brain; Complex I; Mitochondria; Oxidative Stress
ID Code:40665
Deposited On:24 May 2011 13:53
Last Modified:24 May 2011 13:53

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