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.
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