Preliminary Safety Assessment of New Azinesulfonamide Analogs of Aripiprazole using Prokaryotic Models

Abstract

IntroductionOver the last decades the involvement of reactive oxygen species (ROS) in the molecular mechanisms related to psychiatric disorders such as depression or schizophrenia became evident. [1][2][3] In rat models of depression a decreased activity of antioxidant enzymes such as glutathione peroxidase (GSH-Px) followed by increased lipid peroxidation were observed. [4][5][6] Furthermore, in patients with depression the elevated plasma ROS levels were observed to effectively amplify oxidative stress.

Cytotoxic Effects of Aripiprazole on Mkn45 and Nih3t3 Cell Lines and Genotoxic Effects on Human Peripheral Blood Lymphocytes

“…The genetic damage caused by aripiprazole at concentrations below 200 μM was much less than cisplatin, indicating that it could be studied more widely due to its low genotoxicity. The results of our findings in this regard coincided with the work of other researchers (22,23) . The mutagenic and antimutagenic effects of some quinoline-and isoquinolinesulfonamide analogs of aripiprazole were evaluated and their…”

“…The IC 50 of aripiprazole on MKN45 cell line and NIH3T3 cell line was calculated 21.36 μg/mL and 54.17 μg/mL respectively. However, the IC 50 of cisplatin on MKN45 was 12.49 μg/mL and on NIH3T3 results showed that newly synthesized azinesulfonamide analogs of aripiprazole might be considered as genotoxically safe as they do not display mutagenic activity on the tester strains (22) . In addition, genetic toxicity of 545 medications including aripiprazole were studied by using information from 1999 to 2008.…”