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-HT(2) and a dopamine D(2) 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-HT(2) receptor agonist, it is postulated to be mediated by serotonin 5-HT(2) receptors. These findings suggest that AD-5423 would be clinically effective against both the positive and negative symptoms of schizophrenia.
Nagai
T
T
Department of Neuropsychopharmacology, Nagoya University Graduate School of Medicine, Japan.
Noda
Y
Y
Une
T
T
Furukawa
K
K
Furukawa
H
H
Kan
Q M
QM
Nabeshima
T
T
D000818:Animals; D004195:Disease Models, Animal; D007103:Immobilization / Q000502:physiology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010622:Phencyclidine / Q000633:toxicity*; D010879:Piperazines / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D012559:Schizophrenia / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology
D010879:Piperazines; D010880:Piperidines; C079310:blonanserin; D010622:Phencyclidine