阿匹替奈

化合物

阿匹替奈INN:apimostinel;开发代号:GATE-202NRX-1074AGN-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]

阿匹替奈
临床资料
其他名称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
药物类别英语Drug classNMDA受体调节剂英语NMDA receptor modulator
法律规范状态
法律规范
  • Investigational New Drug
识别信息
  • (2R)-1-[(2S)-1-[(2S,3R)-2-Amino-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]-N-[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]-2-benzylpyrrolidine-2-carboxamide
CAS号1421866-48-9
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard英语CompTox Chemicals Dashboard (EPA)
化学信息
化学式C25H37N5O6
摩尔质量503.60 g·mol−1
3D模型(JSmol英语JSmol
  • C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N2CCC[C@@]2(Cc3ccccc3)C(=O)N[C@@H]([C@@H](C)O)C(N)=O
  • InChI=1S/C25H37N5O6/c1-15(31)19(26)23(35)29-12-6-10-18(29)22(34)30-13-7-11-25(30,14-17-8-4-3-5-9-17)24(36)28-20(16(2)32)21(27)33/h3-5,8-9,15-16,18-20,31-32H,6-7,10-14,26H2,1-2H3,(H2,27,33)(H,28,36)/t15-,16-,18+,19+,20+,25-/m1/s1
  • Key:DVBUEXCIEIAXPM-PJUQSVSOSA-N

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四肽,但通过添加苄基基团进行了结构修饰英语Molecular modification,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)的分裂拟精神病英语Psychotomimetism作用。[5]

参见

参考资料

  1. ^ Naurex's Novel Antidepressant GLYX-13 Recognized as One of Windhover's Top 10 Neuroscience Projects to Watch. PR Newswire. 31 August 2010. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. ^ 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). 
  6. ^ Allergan Successfully Completes Naurex Acquisition. Allergan plc (新闻稿). PR Newswire. [2016-11-20]. 
  7. ^ Home - Gate Neurosciences. [2022-05-12] (美国英语). 
  8. ^ Clinical trial number NCT02067793 for "Study of Intravenous NRX-1074 in Patients With Major Depressive Disorder" at ClinicalTrials.gov
  9. ^ 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. 

外部链接