A tetrahydropyrimidine derivative demonstrates neuroprotection against ketamine-induced schizophrenia through moderating oxidative and inflammatory markers.

Schizophrenia impacts individuals' cognition, perceptions, behavior and memory and influences almost 1-1.5% of the global population. It is a psychotic disorder possibly caused by high levels of immunostimulants as well as oxygen-derived free radicals in the blood and CSF. As observed in the studies that pyrimidine derivatives (THP) have promising potential to act as anti-inflammatory agents, therefore these may be helpful in treating schizophrenia. So, this study evaluated the preventive potential of THP in treating schizophrenia induced by ketamine. The mice were segregated in six groups, normal control received 0.5% CMC 1 ml/kg I.P.), disease control and other groups received ketamine 10 mg/kg I.P. Clozapine (1 mg/kg I.P.) served as standard drug. Other groups received THP (10 mg/kg/day I.P.), THP (15 mg/kg/day I.P.) and THP (20 mg/kg/day I.P.). Study was designed as a preventive trial spanning 21-days with initial 14 days treatment, followed by a subsequent 7-day ketamine administration. The study demonstrated that the improvement of positive, negative and cognitive symptoms in THP-treated animals by significantly reducing stereotypic behaviors and inactivity in forced swim and tail suspension tests, and accelerating center time in Open field test and number of entries and alteration in Y-maze test. Oxidative stress in schizophrenic mice was also managed by marked elevation in SOD and CAT levels, and the parameters like GSH, MDA and nitrite contents were significantly reduced. In addition, inflammatory markers such as TNF-α, IL-6, NF-κB and MAP-K were significantly reduced. Furthermore, gene expression showed significant incline in BDNF levels, after THP administration in schizophrenic mice. Overall, the study disclosed THP as an effective compound in mitigating the symptoms of schizophrenia, however further study is needed to evaluate its toxicity profile.