阿匹替奈
化合物
阿匹替奈(INN:apimostinel;开发代号:GATE-202、NRX-1074、AGN-241660)是一种正在研究的抗抑郁药,可作为NMDA受体的新型选择性调节剂。[1][2][3][4]目前,Gate Neurosciences正在开发该药物,用于重度抑郁症的急性治疗。该药物此前由此前Naurex和艾尔建开发。[5][6][7]截至2015年2月,阿匹替奈的静脉制剂已完成针对重度抑郁症的IIa期临床试验。[5][8]
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其他名稱 | NRX-1074、AGN-241660、苏氨酰脯氨酰-2R-(2-苄基)-脯氨酰苏氨酸酰胺 |
给药途径 | 口服 |
藥物類別 | NMDA受体调节剂 |
法律規範狀態 | |
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识别信息 | |
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CAS号 | 1421866-48-9 |
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CompTox Dashboard (EPA) | |
化学信息 | |
化学式 | C25H37N5O6 |
摩尔质量 | 503.60 g·mol−1 |
3D模型(JSmol) | |
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与雷帕替奈(GLYX-13)类似,其作用机制通过NMDA受体上的独特结合位点(独立于甘氨酸位点)发挥作用,以调节受体活性并增强NMDA受体介导的突触可塑性。[9]然而,阿匹替奈的体外效力是雷帕替奈的1000倍,因此它可以作为雷帕替奈的改进型后续药物。[2][5]与雷帕替奈相似,阿匹替奈是一种酰胺化四肽,但通过添加苄基基团进行了结构修饰,以增强其代谢稳定性和药代动力学特征。该药物在抑郁症的临床前模型中显示出快速而有效的抗抑郁作用。[5]此外,阿匹替奈具有良好的耐受性,并且缺乏NMDA受体拮抗剂(如氯胺酮)的分裂样拟精神病作用。[5]
参见
参考资料
- ^ Naurex's Novel Antidepressant GLYX-13 Recognized as One of Windhover's Top 10 Neuroscience Projects to Watch. PR Newswire. 31 August 2010.
- ^ 2.0 2.1 Henter ID, Park LT, Zarate CA. Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status. CNS Drugs. May 2021, 35 (5): 527–543. PMC 8201267 . PMID 33904154. doi:10.1007/s40263-021-00816-x.
- ^ Donello JE, Banerjee P, Li YX, Guo YX, Yoshitake T, Zhang XL, et al. Positive N-Methyl-D-Aspartate Receptor Modulation by Rapastinel Promotes Rapid and Sustained Antidepressant-Like Effects. The International Journal of Neuropsychopharmacology. March 2019, 22 (3): 247–259. PMC 6403082 . PMID 30544218. doi:10.1093/ijnp/pyy101.
- ^ Hayley S, Litteljohn D. Neuroplasticity and the next wave of antidepressant strategies. Frontiers in Cellular Neuroscience. November 2013, 7: 218. PMC 3834236 . PMID 24312008. doi:10.3389/fncel.2013.00218 .
- ^ 5.0 5.1 5.2 5.3 5.4 Naurex Reports Positive Top-Line Phase 2b Results for Novel Antidepressant GLYX-13 and Advances NRX-1074 into Phase 2 Depression Study. PR Newswire. 6 May 2014. (原始内容存档于14 July 2014).
- ^ Allergan Successfully Completes Naurex Acquisition. Allergan plc (新闻稿). PR Newswire. [2016-11-20].
- ^ Home - Gate Neurosciences. [2022-05-12] (美国英语).
- ^ Clinical trial number NCT02067793 for "Study of Intravenous NRX-1074 in Patients With Major Depressive Disorder" at ClinicalTrials.gov
- ^ Donello JE, Banerjee P, Li YX, Guo YX, Yoshitake T, Zhang XL, et al. Positive N-Methyl-D-Aspartate Receptor Modulation by Rapastinel Promotes Rapid and Sustained Antidepressant-Like Effects. The International Journal of Neuropsychopharmacology. March 2019, 22 (3): 247–259. PMC 6403082 . PMID 30544218. doi:10.1093/ijnp/pyy101.