S 17092:一种脯氨酸内肽酶抑制剂作为治疗记忆障碍的潜在药物。临床前和临床研究

Philippe Morain, Pierre Lestage, Guillaume De Nanteuil, Roeline Jochemsen, Jean-Loïc Robin, David Guez, Pierre-Alain Boyer
{"title":"S 17092:一种脯氨酸内肽酶抑制剂作为治疗记忆障碍的潜在药物。临床前和临床研究","authors":"Philippe Morain,&nbsp;Pierre Lestage,&nbsp;Guillaume De Nanteuil,&nbsp;Roeline Jochemsen,&nbsp;Jean-Loïc Robin,&nbsp;David Guez,&nbsp;Pierre-Alain Boyer","doi":"10.1111/j.1527-3458.2002.tb00214.x","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Any treatment that could positively modulate central neuropeptides levels would provide a promising therapeutic approach to the treatment of cognitive deficits associated with aging and/or neurodegenerative diseases. Therefore, based on the activity in rodents, S 17092 (2S,3aS,7aS)-1 ([(R.R)-2-phenylcyclopropyl]carbonyl)-2-[(thiazolidin-3-yl)car-bonyl]octahydro-<i>1H</i>-indole) has been selected as a potent inhibitor of cerebral prolyl-endopeptidase (PEP). By retarding the degradation of neuroactive peptides, S 17092 was successfully used in a variety of memory tasks. These tasks explored short-term, long-term, reference and working memory in aged mice, as well as in rodents and monkeys with chemically induced amnesia or spontaneous memory deficits. S 17092 has also been safely administered to humans, and showed a clear peripheral expression of its mechanism of action through its inhibitory effect upon PEP activity in plasma. S 17092 exhibited central effects, as evidenced by EEG recording in healthy volunteers, and could improve a delayed verbal memory task. Collectively, the preclinical and clinical effects of S 17092 have suggested a promising role for this compound as an agent for the treatment of cognitive disorders associated with cerebral aging.</p>\n </div>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"8 1","pages":"31-52"},"PeriodicalIF":0.0000,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2002.tb00214.x","citationCount":"98","resultStr":"{\"title\":\"S 17092: A Prolyl Endopeptidase Inhibitor as a Potential Therapeutic Drug for Memory Impairment. Preclinical and Clinical Studies\",\"authors\":\"Philippe Morain,&nbsp;Pierre Lestage,&nbsp;Guillaume De Nanteuil,&nbsp;Roeline Jochemsen,&nbsp;Jean-Loïc Robin,&nbsp;David Guez,&nbsp;Pierre-Alain Boyer\",\"doi\":\"10.1111/j.1527-3458.2002.tb00214.x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Any treatment that could positively modulate central neuropeptides levels would provide a promising therapeutic approach to the treatment of cognitive deficits associated with aging and/or neurodegenerative diseases. Therefore, based on the activity in rodents, S 17092 (2S,3aS,7aS)-1 ([(R.R)-2-phenylcyclopropyl]carbonyl)-2-[(thiazolidin-3-yl)car-bonyl]octahydro-<i>1H</i>-indole) has been selected as a potent inhibitor of cerebral prolyl-endopeptidase (PEP). By retarding the degradation of neuroactive peptides, S 17092 was successfully used in a variety of memory tasks. These tasks explored short-term, long-term, reference and working memory in aged mice, as well as in rodents and monkeys with chemically induced amnesia or spontaneous memory deficits. S 17092 has also been safely administered to humans, and showed a clear peripheral expression of its mechanism of action through its inhibitory effect upon PEP activity in plasma. S 17092 exhibited central effects, as evidenced by EEG recording in healthy volunteers, and could improve a delayed verbal memory task. Collectively, the preclinical and clinical effects of S 17092 have suggested a promising role for this compound as an agent for the treatment of cognitive disorders associated with cerebral aging.</p>\\n </div>\",\"PeriodicalId\":94307,\"journal\":{\"name\":\"CNS drug reviews\",\"volume\":\"8 1\",\"pages\":\"31-52\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2006-06-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1111/j.1527-3458.2002.tb00214.x\",\"citationCount\":\"98\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CNS drug reviews\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2002.tb00214.x\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS drug reviews","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2002.tb00214.x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 98

摘要

任何能够积极调节中枢神经肽水平的治疗方法都将为治疗与衰老和/或神经退行性疾病相关的认知缺陷提供一种有希望的治疗方法。因此,基于在啮齿动物体内的活性,我们选择s17092 (2S,3aS,7aS)-1 ([(R.R)-2-苯基环丙基]羰基)-2-[(噻唑烷-3-基)羰基]八氢- 1h -吲哚)作为脑脯氨酸内肽酶(PEP)的有效抑制剂。通过延缓神经活性肽的降解,s17092成功地用于各种记忆任务。这些任务探索了老年小鼠、啮齿类动物和猴子的短期、长期、参考和工作记忆,这些小鼠具有化学诱导的健忘症或自发性记忆缺陷。S 17092也已安全用于人体,并通过其对血浆PEP活性的抑制作用显示出其作用机制的明确外周表达。健康志愿者的脑电图记录证明,s17092表现出中枢效应,可以改善延迟的言语记忆任务。综上所述,s17092的临床前和临床效果表明,该化合物有望作为一种治疗脑衰老相关认知障碍的药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
S 17092: A Prolyl Endopeptidase Inhibitor as a Potential Therapeutic Drug for Memory Impairment. Preclinical and Clinical Studies

Any treatment that could positively modulate central neuropeptides levels would provide a promising therapeutic approach to the treatment of cognitive deficits associated with aging and/or neurodegenerative diseases. Therefore, based on the activity in rodents, S 17092 (2S,3aS,7aS)-1 ([(R.R)-2-phenylcyclopropyl]carbonyl)-2-[(thiazolidin-3-yl)car-bonyl]octahydro-1H-indole) has been selected as a potent inhibitor of cerebral prolyl-endopeptidase (PEP). By retarding the degradation of neuroactive peptides, S 17092 was successfully used in a variety of memory tasks. These tasks explored short-term, long-term, reference and working memory in aged mice, as well as in rodents and monkeys with chemically induced amnesia or spontaneous memory deficits. S 17092 has also been safely administered to humans, and showed a clear peripheral expression of its mechanism of action through its inhibitory effect upon PEP activity in plasma. S 17092 exhibited central effects, as evidenced by EEG recording in healthy volunteers, and could improve a delayed verbal memory task. Collectively, the preclinical and clinical effects of S 17092 have suggested a promising role for this compound as an agent for the treatment of cognitive disorders associated with cerebral aging.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
ERRATUM Cortagine: Behavioral and Autonomic Function of the Selective CRF Receptor Subtype 1 Agonist Guanfacine and Guanfacine Extended Release: Treatment for ADHD and Related Disorders Pharmacology of the β-Carboline FG-7142, a Partial Inverse Agonist at the Benzodiazepine Allosteric Site of the GABAA Receptor: Neurochemical, Neurophysiological, and Behavioral Effects AUTHOR INDEX FOR VOLUME 13
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1