Quinpirole, 8-OH-DPAT and ketanserin modulate catalepsy induced by high doses of atypical antipsychotics

The effect of the selective dopamine D-2 receptor agonist quinpirole, the s elective 5-HT1A receptor agonist 8-OH-DPAT and the selective 5-HT2A recepto r antagonist ketanserin on catalepsy induced by atypical antipsychotics clo zapine, risperidone, olanzapine and sertindole at higher doses,was studied in mts. Haloperidol (0.5, 1 and 2 mg/kg), clozapine (50 and 75 mg/kg) and o lanzapine (15 and 30 mg/kg) produced catalepsy dose-dependently while serti ndole at closes up to 40 mg/kg failed to produce catalepsy in rats. However , sertindole (15, 30 and 45 mg/kg) produced a cataleptic effect in mice in a dose-dependent manner. At a high dose (5 mg/kg), risperidone produced cat alepsy in rats. Quinpirole (0.05 and 0.1 mg/kg) reversed the cataleptic eff ect of haloperidol (2 mg/kg), risperidone (5 mg/kg), olanzapine (30 mg/kg) and sertindole (45 mg/kg). Quinpirole (0.05 and 0.1 mg/kg) reversed clozapi ne (75 mg/kg)-induced catalepsy. 8-OH-DPAT (0.15 and 0.3 mg/kg) dose-depend ently reversed catalepsy induced by haloperidol (2 mg/kg) and risperidone ( 5 mg/kg) without affecting the cataleptic effect of olanzapine. However; th e higher dose (0.45 mg/kg) of 8-OH-DPAT reversed it significantly 8-OH-DPAT (0.3 mg/kg) reversed clozapine (75 mg/kg)-induced catalepsy? 8-OH-DPAT(0.1 5, 0.3 and 0.45 mg/kg) failed to reverse sertindole-induced catalepsy. Keta nserin (0.75 and 1.5 mg/kg) completely reversed catalepsy induced by halope ridol (2 mg/kg) and risperidone (5 mg/kg). Ketanserin (0.75 and 1.5 mg/kg) dose-dependently reversed olanzapine (30 mg/kg) and sertindole (45 mg/kg)-i nduced catalepsy without any effect on clozapine (75 mg/kg)-induced catalep sy. A higher dose (3 mg/kg) of ketanserin reversed clozapine-induced catale psy. The present study suggests that atypical antipsychotics show fewer ext rapyramidal symptoms (EPS) due to greater modulation of the serotonergic sy stem. Therefore, an antipsychotic with dopamine D-2/5-HT2A antagonistic act ion and 5-HT1A agonistic action may prove to be superior to the existing an tipsychotics. (C) 1999 Prous Science. All rights reserved.