Suppr超能文献

拉曲匹定,一种治疗阿尔茨海默病和亨廷顿舞蹈症的潜在新型药物。

Latrepirdine, a potential novel treatment for Alzheimer's disease and Huntington's chorea.

作者信息

Sabbagh Marwan N, Shill Holly A

机构信息

Banner Sun Health Research Institute, The Cleo Roberts Center for Clinical Research, 10515 West Santa Fe Drive, Sun City, AZ 85351, USA.

出版信息

Curr Opin Investig Drugs. 2010 Jan;11(1):80-91.

Abstract

Latrepirdine (Dimebon) is a small-molecule compound under development by Medivation Inc and Pfizer Inc for the treatment of Alzheimer's disease and Huntington's chorea. Originally developed and marketed as an antihistamine in Russia, latrepirdine has since demonstrated potential for the treatment of neurodegenerative diseases. Early research suggested that the mechanism of action was centered on AChE inhibition and NMDA antagonism. More recent research questions these early findings, and other mechanisms of action have been proposed and investigated. In phase II clinical trials, latrepirdine demonstrated clinically relevant improvements in patients with Alzheimer's disease and Huntington's chorea. At the time of publication, phase III clinical trials had been initiated. Given the robustness of the phase II clinical data, latrepirdine has a high likelihood of success in phase III trials and in subsequently being granted regulatory approval.

摘要

拉曲匹定(二甲金刚胺)是Medivation公司和辉瑞公司正在研发用于治疗阿尔茨海默病和亨廷顿舞蹈症的一种小分子化合物。拉曲匹定最初在俄罗斯研发并作为抗组胺药上市,后来已显示出治疗神经退行性疾病的潜力。早期研究表明其作用机制集中在抑制乙酰胆碱酯酶和拮抗N-甲基-D-天冬氨酸。最近的研究对这些早期发现提出质疑,并提出和研究了其他作用机制。在II期临床试验中,拉曲匹定在阿尔茨海默病和亨廷顿舞蹈症患者中显示出具有临床意义的改善。在发表本文时,III期临床试验已经启动。鉴于II期临床数据的稳健性,拉曲匹定在III期试验中取得成功并随后获得监管批准的可能性很大。

相似文献

3
The rise and fall of Dimebon.
Drug News Perspect. 2010 Oct;23(8):518-23. doi: 10.1358/dnp.2010.23.8.1500435.
4
ACS chemical neuroscience molecule spotlight on dimebon.
ACS Chem Neurosci. 2010 Sep 15;1(9):587-8. doi: 10.1021/cn1000588.
5
Latrepirdine for Alzheimer's disease.
Cochrane Database Syst Rev. 2015 Apr 21;2015(4):CD009524. doi: 10.1002/14651858.CD009524.pub2.
7
8
From anti-allergic to anti-Alzheimer's: Molecular pharmacology of Dimebon.
Curr Alzheimer Res. 2010 Mar;7(2):97-112. doi: 10.2174/156720510790691100.
10
Antihistamine agent Dimebon as a novel neuroprotector and a cognition enhancer.
Ann N Y Acad Sci. 2001 Jun;939:425-35. doi: 10.1111/j.1749-6632.2001.tb03654.x.

引用本文的文献

1
Shedding light on microglial dysregulation in Alzheimer's disease: exploring molecular mechanisms and therapeutic avenues.
Inflammopharmacology. 2025 Feb;33(2):679-702. doi: 10.1007/s10787-024-01598-6. Epub 2024 Nov 28.
3
A Novel Huntington's Disease Assessment Platform to Support Future Drug Discovery and Development.
Int J Mol Sci. 2022 Nov 25;23(23):14763. doi: 10.3390/ijms232314763.
4
Pharmacological modulation of autophagy for Alzheimer's disease therapy: Opportunities and obstacles.
Acta Pharm Sin B. 2022 Apr;12(4):1688-1706. doi: 10.1016/j.apsb.2021.12.009. Epub 2021 Dec 18.
5
Rodent Models of Amyloid-Beta Feature of Alzheimer's Disease: Development and Potential Treatment Implications.
Aging Dis. 2020 Oct 1;11(5):1235-1259. doi: 10.14336/AD.2019.1026. eCollection 2020 Oct.
7
In Vitro Effects of Cognitives and Nootropics on Mitochondrial Respiration and Monoamine Oxidase Activity.
Mol Neurobiol. 2017 Oct;54(8):5894-5904. doi: 10.1007/s12035-016-0121-y. Epub 2016 Sep 23.
8
Novel Sites of Neuroprotective Action of Dimebon (Latrepirdine).
Mol Neurobiol. 2015 Oct;52(2):970-8. doi: 10.1007/s12035-015-9249-4. Epub 2015 Jun 30.
9
Advances in recent patent and clinical trial drug development for Alzheimer's disease.
Pharm Pat Anal. 2014 Jul;3(4):429-47. doi: 10.4155/ppa.14.22.

本文引用的文献

1
Drug development for Alzheimer's disease: where are we now and where are we headed?
Am J Geriatr Pharmacother. 2009 Jun;7(3):167-85. doi: 10.1016/j.amjopharm.2009.06.003.
2
Do cholinergic therapies have disease-modifying effects in Alzheimer's disease?
Alzheimers Dement. 2006 Apr;2(2):118-25. doi: 10.1016/j.jalz.2006.02.001.
3
Methylene blue and dimebon inhibit aggregation of TDP-43 in cellular models.
FEBS Lett. 2009 Jul 21;583(14):2419-24. doi: 10.1016/j.febslet.2009.06.042. Epub 2009 Jun 26.
4
Dimebolin is a 5-HT6 antagonist with acute cognition enhancing activities.
Biochem Pharmacol. 2009 Oct 15;78(8):1035-42. doi: 10.1016/j.bcp.2009.06.021. Epub 2009 Jun 21.
5
Mitochondrial structural and functional dynamics in Huntington's disease.
Brain Res Rev. 2009 Jun;61(1):33-48. doi: 10.1016/j.brainresrev.2009.04.001. Epub 2009 Apr 24.
6
The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer's disease.
J Neurochem. 2009 May;109 Suppl 1(Suppl 1):153-9. doi: 10.1111/j.1471-4159.2009.05867.x.
8
Randomized controlled trial of ethyl-eicosapentaenoic acid in Huntington disease: the TREND-HD study.
Arch Neurol. 2008 Dec;65(12):1582-9. doi: 10.1001/archneur.65.12.1582.
9
Evaluation of Dimebon in cellular model of Huntington's disease.
Mol Neurodegener. 2008 Oct 21;3:15. doi: 10.1186/1750-1326-3-15.
10
Mitochondrial DNA damage is a hallmark of chemically induced and the R6/2 transgenic model of Huntington's disease.
DNA Repair (Amst). 2009 Jan 1;8(1):126-36. doi: 10.1016/j.dnarep.2008.09.004. Epub 2008 Nov 20.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验