Effect of AD-5423 on animal models of schizophrenia: Phencyclidine-induced behavioral changes in mice

The antipsychotic efficacy of AD-5423, which has the properties of both a serotonin 5-HT₂ and a dopamine D₂ receptor antagonist, was evaluated using animal models of schizophrenia. Sensitization to phencyclidine (PCP)-induced hyperlocomotion is considered a model of the positive symptoms of schizophrenia, and was significantly antagonized by AD-5423 and haloperidol. The PCP-induced enhancement of immobility induced by the forced swimming test, a model of the negative symptoms of schizophrenia, was attenuated by AD-5423 but not by haloperidol. Since this attenuated effect of AD-5423 was antagonized by DOI, a serotonin 5-HT₂ receptor agonist, it is postulated to be mediated by serotonin 5-HT₂ receptors. These findings suggest that AD-5423 would be clinically effective against both the positive and negative symptoms of schizophrenia.