Apocynin-Tandospirone Derivatives Suppress Methamphetamine-Induced Hyperlocomotion in Rats with Neonatal Exposure to Dizocilpine.

Accumulating evidence implicates oxidative stress as a potential pathophysiological mechanism of schizophrenia. Accordingly, we synthesized new chemicals using apocynin and tandospirone as lead compounds (, and ). 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 -methyl-d-aspartate receptor antagonist, in the neonatal period. To determine whether , and 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. and , administered for 14 days around the puberty period, ameliorated MAP-induced hyperlocomotion in MK-801-treated rats in the post-puberty period, while suppressed MAP-induced vertical activity. These findings indicate that apocynin-tandospirone derivatives present anti-dopaminergic effects and may alleviate psychotic symptoms of schizophrenia.