Atypical antipsychotic effects of quetiapine fumarate in animal models.
OBJECTIVE
To evaluate the effect of quetiapine fumarate in animal models of schizophrenia and its possibility to induce extrapyramidal side effects (EPSE).


METHODS
The enhancement of immobility in a forced swimming test of mice induced by repeated treatment with phencyclidine and amphetamine swimming "normalization" test of mice were used as animal models of negative and positive symptoms of schizophrenia, respectively. The paw test of rats was used to evaluate the possibility by quetiapine fumarate to induce EPSE.


RESULTS
After treatment with phencyclidine (10 mg.kg-1.d-1, s.c., 14 d), the immobility time in the forced swimming test of mice was increased (P < 0.01). Quetiapine fumarate (20, 40, and 80 mg.kg-1, ig) and clozapine (10 and 30 mg.kg-1, ig) attenuated the enhanced immobility in the forced swimming test induced by repeated treatment with phencyclidine (P < 0.01), whereas haloperidol (0.3 and 1 mg.kg-1, ig) had no effect. In amphetamine swimming "normalization" test, quetiapine fumarate ameliorated the disorder induced by amphetamine in a dose-dependent manner. In paw test, quetiapine fumarate was much less effective in increasing the forelimb retraction time (FRT) than the hindlimb retraction time (HRT). The minimal effective dose (MED) of HRT (MEDHRT) and FRT (MEDFRT) of quetiapine fumarate was 20 mg.kg-1 and 100 mg.kg-1, respectively, and the ratio of MEDFRT to MEDHRT was 5.


CONCLUSIONS
The effects of quetiapine fumarate in these models indicated its clinical effect on schizophrenia with a reduced liability to produce EPSE.
Guan
H J
HJ
Department of Pharmacology I, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China.
Dai
J
J
Zhu
X Z
XZ
D000661:Amphetamine; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000517:prevention & control; D003024:Clozapine / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use; D007103:Immobilization; D008297:Male; D051379:Mice; D010622:Phencyclidine; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000139:chemically induced / Q000188:drug therapy; D012563:Schizophrenia, Paranoid / Q000139:chemically induced / Q000188:drug therapy
D014150:Antipsychotic Agents; D000661:Amphetamine; D010622:Phencyclidine; D003024:Clozapine; D006220:Haloperidol