Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction was written by Platanic Arizanovic, Lena;Nikolic-Kokic, Aleksandra;Brkljacic, Jelena;Tatalovic, Nikola;Miler, Marko;Orescanin-Dusic, Zorana;Vidonja Uzelac, Teodora;Nikolic, Milan;Milosevic, Verica;Blagojevic, Dusko;Spasic, Snezana;Miljevic, Cedo. And the article was included in Journal of Toxicology and Environmental Health, Part A: Current Issues in 2021.Reference of 146939-27-7 This article mentions the following:
Chronic use of atypical antipsychotics may produce hepatic damage. Atypical antipsychotics, including clozapine, sertindole, and ziprasidone, are extensively metabolized by the liver and this process generates toxic-free radical metabolic intermediates which may contribute to liver damage. The aim of this study was to investigate whether clozapine, sertindole, or ziprasidone affected hepatic antioxidant defense enzymes which consequently led to disturbed redox homeostasis. The expression and activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and glutathione-S-transferases (GST) were measured in rat livers at doses corresponding to human antipsychotic therapy. Clozapine increased activity of SOD types 1 and 2, GR and GST, but reduced CAT activity. Sertindole elevated activities of both SODs. In ziprasidone-treated rats only decreased CAT activity was found. All three antipsychotics produced mild-to-moderate hepatic histopathol. changes categorized as regenerative alterations. No apparent signs of immune cell infiltration, microvesicular or macrovesicular fatty change, or hepatocytes in mitosis were observed In conclusion, a 4-wk long daily treatment with clozapine, sertindole, or ziprasidone altered hepatic antioxidant enzyme activities and induced histopathol. changes in liver. The most severe alterations were noted in clozapine-treated rats. Data indicate that redox disturbances may contribute to liver dysfunction after long-term atypical antipsychotic drug treatment. In the experiment, the researchers used many compounds, for example, 5-(2-(4-(Benzo[d]isothiazol-3-yl)piperazin-1-yl)ethyl)-6-chloroindolin-2-one (cas: 146939-27-7Reference of 146939-27-7).
5-(2-(4-(Benzo[d]isothiazol-3-yl)piperazin-1-yl)ethyl)-6-chloroindolin-2-one (cas: 146939-27-7) belongs to isothiazole derivatives. Isothiazoles and benzisothiazoles are usually liquids or low-melting-point solids; polar substituents increase the melting points because of the possibility of hydrogen bonding and other interactions in the crystalline state. In general, isothiazole undergoes nitration in the presence of HNO3, sulfuric acid, and sulfonation by using sulfuric acid under thermal conditions to generate corresponding 4-nitro- and 4-sulfonic acid derivatives, respectively.Reference of 146939-27-7
Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com