齐洛那平临床前体外及体内抗精神分裂症药效的初步研究  

Preliminary preclinical study on antischizophrenia efficacy of zicronapine in vitro and in vivo

作　　者：魏雅芹 徐祥清[2] 邱印利[2] 于民权[2] Wei Yaqin;Xu Xiangqing;Qiu Yinli;Yu Minquan(School of Pharmacy,Xuzhou Medical University,Xuzhou 221004,China;Jiangsu Nhwa Pharmaceutical Co.,Ltd Jiangsu Provincial Key Laboratory of CNS Drugs,Xuzhou 221000,China)

机构地区：[1]徐州医科大学药学院,徐州221004 [2]江苏恩华药业股份有限公司江苏省中枢神经药物研究重点实验室,徐州221000

出　　处：《中华精神科杂志》2022年第6期451-458,共8页Chinese Journal of Psychiatry

摘　　要：目的考察齐洛那平对不同精神分裂症动物模型的药效及其对多巴胺D_(1)、D_(2)等受体的体外亲和力。方法纳入雄性SPF级ICR小鼠324只,雄性SPF级Wistar大鼠72只及SPF级SD大鼠雌雄各10只为研究对象。(1)取100只ICR小鼠分为10组:空白组(溶媒+生理盐水,简称Veh+NS),模型组(Veh+APO 1 mg/kg),利培酮(0.03、0.10、0.30、1.00 mg/kg,灌胃)+APO组,齐洛那平(0.3、1.0、3.0、10.0 mg/kg,灌胃)+APO组;每组10只,观察齐洛那平对小鼠攀爬行为的影响。(2)取84只ICR小鼠分为10组:空白组(Veh+NS),模型组(Veh+MK-8010.3 mg/kg),利培酮(0.01、0.03、0.10、0.30 mg/kg,灌胃)+MK-801组,齐洛那平(0.3、1.0、3.0、10.0 mg/kg,灌胃)+MK-801组;每组8~10只,观察齐洛那平对MK-801诱导小鼠高活动行为的影响。(3)取70只ICR小鼠分为7组:空白组(Veh),利培酮0.3、1.0及3.0 mg/kg组(灌胃),齐洛那平15、27及45 mg/kg组(灌胃),每组10只,观察小鼠在给药后30、60及90 min时保持僵住不动的时间。(4)取72只Wistar大鼠进行条件回避反应训练,将训练成功的大鼠分为7组:空白组(Veh),齐洛那平20、40及60 mg/kg组,利培酮0.2、0.4及0.8 mg/kg组,每组5~6只,考察齐洛那平对大鼠回避反应次数的影响。(5)取70只ICR小鼠,颈部皮下注射给予PCP(5 mg/kg)造模后,将小鼠分为空白组(Veh+NS),模型组(Veh+PCP),利培酮0.05 mg/kg+PCP组,齐洛那平(0.5、1.0、2.0 mg/kg)+PCP组,每组10~12只,考察齐洛那平对PCP诱导小鼠新物体识别障碍的影响。(6)将20只SD大鼠(雌雄各半)断头取脑,并制备5-HT_(2A)及5-HT_(2C)受体膜,取表达CHO-D_(1)、D_(2)及5-HT_(6)受体的细胞株制备D_(1)、D_(2)及5-HT_(6)受体膜,通过放射性配体受体结合的实验方法,考察齐洛那平对D_(1)、D_(2)、5-HT_(2A)、5-HT_(6)及5-HT_(2C)的亲和力。组间计量资料比较采用单因素方差分析,计数资料采用非参数U检验。结果(1)与模型组比较,齐洛那平剂量3.0及10.0 mg/kg可显著抑制APO诱导的小鼠攀爬行�Objective To investigate the efficacy of zicronapine on different animal models of schizophrenia and its affinity for dopamine D_(1) and D_(2) receptors in vitro.Methods A total of 324 male SPF ICR mice,72 male SPF Wistar rats,and 10 male and female each SPF SD rats were included in the study.(1)One hundred ICR mice were divided into 10 groups:Blank group(solvent+normal saline,Veh+NS),model group(Veh+APO 1 mg/kg),risperidone(0.03,0.10,0.30,1.00 mg/kg,gavage)+APO group,and zicronapine(0.3,1.0,3.0,10.0 mg/kg,gavage)+APO group;The effect of zicronapine on the climbing behavior of mice was observed.(2)Eighty-four ICR mice were divided into 10 groups:Blank group(Veh+NS),model group(Veh+MK-8010.3 mg/kg),risperidone(0.01,0.03,0.10,0.30 mg/kg,gavage)+MK-801 group,and zicronapine(0.3,1.0,3.0,10.0 mg/kg,gavage)+MK-801 group;8-10 rats were allocated in each group to observe the effect of zicronapine on MK-801-induced hyperactivity behavior in mice.(3)Seventy mice were divided into 7 groups:Blank group(Veh),risperidone 0.3,1.0 and 3.0 mg/kg groups(gavage),and zicronapine15,27 and 45 mg/kg groups(gavage),with 10 mice in each group.The maintaining immobilized time of rats was observed at 30 min,60 min and 90 min after administration.(4)A total of 72 Wistar rats were selected for CAR training,and the successfully trained rats were divided into 7 groups:blank group,zicronapine20,40 and 60 mg/kg groups,risperidone 0.2,0.4 and 0.8 mg/kg groups,with 5 to 6 rats in each group.The effects of zicronapine on avoidance response times of rats were investigated.(5)Seventy ICR mice were divided into blank group(Veh+NS),model group(Veh+PCP)and risperidone 0.05 mg/kg+PCP group.The effects of zicronapine(0.5,1.0,2.0 mg/kg)+PCP groups on novel object recognition disorder in mice were investigated.(6)The affinity of zicronapine to D_(1),D_(2),5-HT_(2A),5-HT_(6) and 5-HT_(2C) was investigated by radiolig and receptor binding assay.One-way analysis of variance was used for measurement data,and non-parametric U test was used for count data.Results

关 键 词：精神分裂症 抗精神病药 齐洛那平 多巴胺受体 

分 类 号：R965[医药卫生—药理学]