Journal
JOURNAL OF PERSONALIZED MEDICINE
Volume 12, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/jpm12030366
Keywords
apocynin; tandospirone; antioxidant; MK-801; locomotion; animal model; schizophrenia
Funding
- Japan Society for the Promotion of Science KAKENHI Grant [21K07511]
- Intramural Research Grants for Neurological and Psychiatric Disorders of NCNP [3-1]
- Japan Health Research Promotion Bureau Grants [2021-B-01]
- KAKENHI Grant [20H03610]
- Grants-in-Aid for Scientific Research [20H03610, 21K07511] Funding Source: KAKEN
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Oxidative stress is implicated as a potential mechanism of schizophrenia. Researchers synthesized novel compounds and found that they exhibited antipsychotic properties, indicating their potential to alleviate symptoms of schizophrenia.
Accumulating evidence implicates oxidative stress as a potential pathophysiological mechanism of schizophrenia. Accordingly, we synthesized new chemicals using apocynin and tandospirone as lead compounds (A-2, A-3 and A-4). These novel compounds decreased reactive oxygen species (ROS) concentrations in vitro and reversed decreases in glutathione levels in the medial prefrontal cortex of rats transiently exposed to MK-801, an N-methyl-D-aspartate receptor antagonist, in the neonatal period. To determine whether A-2, A-3 and A-4 show behavioral effects associated with antipsychotic properties, the effects of these compounds on methamphetamine (MAP)-induced locomotor and vertical activity were examined in the model rats. A-2 and A-3, administered for 14 days around the puberty period, ameliorated MAP-induced hyperlocomotion in MK-801-treated rats in the post-puberty period, while A-4 suppressed MAP-induced vertical activity. These findings indicate that apocynin-tandospirone derivatives present anti-dopaminergic effects and may alleviate psychotic symptoms of schizophrenia.
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