Novel Arecoline Derivatives as Muscarinic Receptor 1 Agonists for Alzheimer's Dementia Models

来源 :中国上海第七届国际新药发明科技年会 | 被引量 : 0次 | 上传用户:spsnake
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
  The cholinergic deficit in Alzheimers disease (AD) patients brain has intensified research efforts to test cholinomimetic approaches for efficacy in AD therapy.Various therapies may be of potential clinical use in AD.Among these are cholinergic agents including muscarinic agonists,acetylcholinesterase inhibitors,and acetylcholine releasing agents.One of the muscarinic agonists tested in AD is arecoline and its bioisosters,which are widely,explored as muscarinic receptor 1 agonist (M1 receptor agonist) in AD research.In this regard,we have synthesized five and six membranes heterocyclic ring system attached arecoline basic nucleus (N-methyl tetrahydropyridines) at 3rd position.Subsequently the synthesized arecolines derivatives were subjected to in vitro muscarinic receptor 1 binding affinity studies using male wistar rat brain synaptosomal membrane (cerebral cortex) and also cell line culture studies and extended this in vitro studies to in vivo pharmacological evaluation of memory and learning in male wistar rats (Rodent memory evaluation,plus and Y maze studies).Some of our synthesized molecules have shown very potent M1 receptor agonist activity and significantly elevated the basal IP3 levels in vitro and also have decreased beta-amyloid (Abeta40 and Abeta42) deposition in cell lines culture.These molecules have also shown very good antidementia activity in rat dementia model.Molecules with electron donating group as a substitute,has shown very good affinity towards the M1 receptor in vitro and has also elicited beneficial effects in vivo memory and learning models.
其他文献
邢台县丘陵区有丰富的野生酸枣资源,利用酸枣改接梨枣,投资小,见效快,收益高,能充分发挥现有的资源优势。1998年,邢台县从中国林业科学院引进大枣新品种──梨枣,共引进接穗30万根,在滹沱、
茄子嫁接已成为深局冬棚(室)茄子 栽培中的关键技术措施。但据调查:在 生产实践应用中,较普遍的存在着关 键技术不到位,茄苗成活率低,茄苗不 壮,甚至导致栽培失败等问题。那么怎 样
  Multiplex diagnostics apply advanced molecular biology techniques to clinical challenges in patient care.As technology advances,the technology becomes relia
会议
  This talk will discuss the following topics:● Introduction ● Polymorphism characterization ● New form generation and identification ● Amorphous form sta
  Background During the past 10 years there has been growing interest in the role of mitochondrial dysfunction in many diseases,including heart disease,metabo
会议
  There is an urgent need for biomarker-based tests that enable a more accurate and early diagnosis of Alzheimer disease (AD).Recently it has been shown that
会议
接过冠军奖杯时,这个27岁的非洲年轻人哭了 “魅力”是什么意思?27岁的非洲小伙阿卜杜拉报名参加“佛山魅力大使”比赛的时候,还不认识“魅力”这两个字,心里也完全不知道要
  The main goal of the cancer research is to improve the clinical outcome of cancer patients.At present,we can perform tailor-made chemotherapy,the selection
会议
  Nyctanthus arbortristis Linn.(Family-Oleacea) is a well documented plant.Its various parts are used traditionally folk medicine for treating various disease
会议
说起漫画《八戒外传》,可谓家喻户晓,1989年3月26日在《钱江晚报》开始连载,长达12年,共1700余幅,在国内漫画界创下历史记录。作者“鱼虫笺”其实就是俞志达和他的画友戎念竹