阿匹替奈

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 class）	NMDA受体调节剂（英语：NMDA receptor modulator）
法律规范状态
法律规范	美：Investigational New Drug;
识别信息
	IUPAC命名法 (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	71249967;
ChemSpider	52085607;
UNII	TTT1F11FZB;
KEGG	D11299;
ChEMBL	ChEMBL3545230;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID101031863 ;
化学信息
化学式	C25H37N5O6
摩尔质量	503.60 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES 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 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;

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]

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（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）的分裂样拟精神病（英语：Psychotomimetism）作用。^[5]

参见

泽奎替奈

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.

外部链接

Apimostinel (NRX-1074) - AdisInsight

[PRNewswire2010-1] Naurex's Novel Antidepressant GLYX-13 Recognized as One of Windhover's Top 10 Neuroscience Projects to Watch. PR Newswire. 31 August 2010.

[Henter_2021-2] 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.

[MEDRS_review-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  .

[PRNewswire2014-5] 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.

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