Antischizophrenic effect of dopamine D3 receptor antagonist Y-QA31

来源 :第十五届中国神经精神药理学学术会议 | 被引量 : 0次 | 上传用户:RedLenov
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  OBJECTIVCE Schizophrenia is a chronic, debili tating psychotic mental disorder.Many studies suggest that dopa mine D3 receptor (DAD3R) plays an important role in etioloy of schizophrenia, and selective DAD3 R antagonists may have effects to improve the symptoms of schizophrenia.More important, the DAD3 R antagonists result in less or no extrapyramidal side effect (EPS).Therefore, the present study is aimed to evaluate the pharmacological effects of Y-QA31 which was found to be a high ly selective DAD3 R antagonist, hoping to develop new potential APDs.METHODS We use the animals models, including methamphetamine (MA) or dizocilpine (MK-801) induced hy peractivity, apomorphine-induced climbing, the disruption of prepulse Inhibition elicited by MA, conditioned avoidance re sponding and apomorphine-induced hypothermia to evaluate the effects of Y-QA31 on the treatment of schizophrenia.Meanwhile,the induction of catalepsy of Y-QA31 was also observed in mice.RESULTS Y-QA31 (20-40 mg·kg-1, po) effectively inhib ited conditioned avoidance responding in mice, the hyperactivity induced by MA or MK-801, and apomorphine-induced hypother mia in mice by dose-dependence.Y-QA31 (5 mg·kg-1, po)could also inhibit the reduction of prepulse Inhibition elicited by MA in mice.Morerover, Y-QA31 (80 mg·kg-1, po) could also inhibit apomorphine-induced climbing in mice.Y-QA31 did not induce catalepsy when its dose increased to 200 rmg· kg-1 po,suggesting the EPS of Y-QA31 was very low.CONCLUSION The above results indicated Y-QA31 exhibited the therapeutic effects on positive symptoms of schizophrenia with low EPS, and further suggested that DAD3 R is the potential target in the treat ment of schizophrenia.
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