Pro-oxidant activity of zuclopenthixol in vivo: differential effect of the drug on brain oxidative status of scopolamine-treated rats.
Several clinical studies implicated oxidative stress in the pathophysiology of both psychosis and dementia. As dementia is commonly associated with psychosis, antipsychotic medications are of importance in the pharmacotherapy of dementia particularly as a number of antipsychotics were reported to demonstrate neuronal pro-oxidant and/or antioxidant properties. Impairment of learning and memory, as the most characteristic manifestation of dementia, could be induced in experimental animals by acute administration of scopolamine (SCO) with a resultant elevation in brain oxidative status. This study investigated the potential pro-oxidant and/or antioxidant activity of the antipsychotic drug zuclopenthixol acetate, as its effect on brain oxidative status has yet to be evaluated. A 2 x 3 between-subjects factorial design was used to investigate the simultaneous and interactive effects of zuclopenthixol (0.7 and 1.4 mg/kg i.p.) and SCO on rat brain malondialdehyde, glutathione, glutathione peroxidase and superoxide dismutase levels/activities. Results revealed a significant pro-oxidant effect for both zuclopenthixol and SCO alone conditions. In addition, combined treatment of zuclopenthixol and SCO was found to be significantly different compared to either treatment conditions with regard to their effect on different brain oxidative stress indices. Such findings may have valuable implications in the pharmacotherapy of both psychosis and dementia.
Khalifa
Amani E
AE
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. amani@ims.com.eg
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation; D003006:Clopenthixol / Q000494:pharmacology*; D004338:Drug Combinations; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
D014150:Antipsychotic Agents; D004338:Drug Combinations; D018727:Muscarinic Antagonists; D008315:Malondialdehyde; D003006:Clopenthixol; D012601:Scopolamine; D010088:Oxidoreductases; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione