化合物XZ07抗精神分裂症活性及作用机制研究  

Effects of compound XZ07 on schizophrenia models in mice and its mechanism

作　　者：魏雅芹[1] 徐祥清[2] 

机构地区：[1]徐州医学院药学院,江苏徐州221002 [2]江苏恩华药业股份有限公司技术中心药理室,江苏徐州221007

出　　处：《徐州医学院学报》2012年第3期154-157,共4页Acta Academiae Medicinae Xuzhou

摘　　要：目的 了解化合物XZ07抗精神分裂症活性,并对其作用机制进行初步探讨.方法 采用阿扑吗啡诱导小鼠攀爬模型及地卓西平（MK-801 ）诱导小鼠高活动性模型,观察化合物XZ07对模型小鼠攀爬行为及活动总路程的影响来了解化合物XZ07抗精神分裂活性;大鼠断头取脑后提取脑内多巴胺（D2）、5-羟色胺1A（5-HT1A）及5-羟色胺2A（5-HT2A）受体蛋白,采用体外配体受体结合试验,通过观察化合物XZ07与D2、5-HT1A及5-HT2A受体的亲和性来初步了解其作用机制.结果 化合物XZ07高、中、低3个剂量都能剂量依赖性地抑制阿朴吗啡小鼠攀爬行为,显著减少小鼠攀爬试验中评分（P〈0.01）;化合物XZ07高、中剂量能显著减少MK-801诱导的高活动性小鼠90 min内总活动路程（P〈0.01）;体外受体试验发现,化合物XZ07与D2、5-HT1A及5-HT2A受体均具有较高的亲和力.结论 化合物XZ07具有较好的抗精神分裂活性,有望开发成抗精神分裂症的新药,其作用机制可能与D2、5-HT1A及5-HT2A受体有关.Objective To investigate the effects of compound XZ07 on schizophrenia models in mice and its mecha- nism. Methods Using apomorphine -induced mice climbing model and MK- 801 -induced mice hyperlocomotion model to examine the effects of compound XZ07 on schizophrenia. The affinities of compound XZ07 on rat D2 and 5 - HT1A, 5 -HTzA receptors were evaluated in vitro binding assays using the radioligands [ 3 HI 8 -OH -DPAT , [ 3H ] - Ketanserin, [ 3 H ] - Spiperone,respectively. Results Compared with model group, compound XZ07 dose - dependently decreased the climbing scores in apomorphine - induced climbing test, meanwhile it also significantly inhibited the spon- taneous activity （P 〈 0.01 ） in MK - 801 - induced hyperlocomotion test at the dose of 10 and 30 mg/kg, but at low dose （ 3 mg/kg ） it had no affects on the spontaneous activity. At the in vitro binding test compound XZ07 showed high affinity on D2 and 5 - HTIA, 5 - HT2A receptors. Conclusion Compound XZ07 has effects on schizophrenia, its mechanism may be involved in 5 - HTIA, 5 - HT2A and D2 receptors.

关 键 词：精神分裂症 MK-801诱导高活动性 阿扑吗啡诱导攀爬 受体结合试验 

分 类 号：R964[医药卫生—药理学]