Perospirone is a serotonin-dopamine antagonist (SDA) recently developed in Japan as an atypical antipsychotic to be used in the treatment of schizophrenia. The amines and amino acids in the cortex are assumed to play an important role in the cognitive dysfunction of schizophrenia. To investigate the acute effect of perospirone on cognition, we compared perospirone to risperidone and haloperidol by assessing their influence on prepulse inhibition (PPI). Moreover, we studied the effects of these drugs on amine and amino acid contents in the rat cortex. Perospirone had a significant influence: PPI, dopamine turnover and glycine contents increased statistically and serotonin decreased statistically in comparison to control levels. Our results suggest that, of the three antipsychotic drugs, only perospirone promotes cognition, and this ability is associated with increase in dopamine turnover, reduction in serotonin turnover and increase in glycine contents.