新型M受体激动剂MA9701的促智作用  

Effect of anovel muscarinic receptor agonist MA9701 on cognitive improvement

作　　者：崔永耀[1] 冯菊妹[1] 刘慧中[1] 朱亮[1] 荣征星[1] 陆阳[1] 陈红专[1] 

机构地区：[1]上海第二医科大学药物研究所,上海200025

出　　处：《中国临床药理学与治疗学》2003年第5期503-505,共3页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金项目 (№ 30 0 70 86 0 );上海市教委科技发展基金项目(98B5;0 2BZ30 ) ;上海市教委重点学科研究基金项目(№ 9970 2 0 4 )

摘　　要：目的 :观察新型莨菪类化合物MA970 1对小鼠记忆障碍模型的学习与记忆影响 ,以及对大鼠皮层海马组织的M受体动力学特性的影响。方法 :建立小鼠乙醇致记忆再现障碍和东莨菪碱致记忆获得障碍模型 ,用避暗法测定学习与记忆功能。用受体放射配基法测定M受体动力学参数。结果 :与模型组比较 ,MA970 1 3、1 0mg·kg- 1 剂量均可显著延长乙醇致记忆障碍小鼠自明处进入暗处的潜伏期 ,减少错误次数 ,量效曲线呈倒U型 ;MA970 1 5、1 0mg·kg- 1 剂量 ,可使东莨菪碱致记忆获得障碍小鼠的错误次数显著降低 ,而潜伏期无显著延长。MA970 1对大鼠皮层海马组织的M受体具有较强的亲和力 ,其Ki 分别为氧化震颤素、槟榔碱的 6及 2 3倍。结论 :新型莨菪类衍生物MA970 1能明显改善乙醇和东莨菪碱所致小鼠学习与记忆障碍功能 ,其作用可能与激动脑内皮层和海马中枢M胆碱受体有关。AIM: To evaluate the cognitive improvement of MA9701, a newly synthesized nortropane and its binding properties at muscarinic receptor in the cortex and hippocampus. METHODS: Learning and memory performance was studied using step through test in mice. The kinetics for the binding to muscarinic receptor in the cortex and hippocampus were determined using QNB. RESULTS: Compared with ethanol model group, MA9701 (3 and 10 mg·kg -1 ) obviously decreased the number of errors in five minutes and prolonged the footshock passive avoidance latency in a dose dependent and U shaped manner. And also, MA9701 (5 and 10 mg·kg -1 ) could significantly reverse scopolamine induced memory impairment. Radioligand binding assays showed that MA9701 had 6 and 23 times higher affinities to muscarinic receptor in the cortex and hippocampus than oxo and arecloine, respectively. CONCLUSION: Novel nortropane MA9701 might exert potent cognitive improvement by the activation of muscarinic receptor in the cortex and hippocampus.

关 键 词：药理学 莨菪烷化合物 M受体激动剂 学习与记忆 放射配基分析 

分 类 号：R965[医药卫生—药理学] R971.92[医药卫生—药学]