阿匹替奈

阿匹替奈
臨床資料
其他名稱	NRX-1074、AGN-241660、蘇氨醯脯氨醯-2R-(2-苄基)-脯氨醯蘇氨酸醯胺
給藥途徑	口服
藥物類別（英語：Drug class）	NMDA受體調節劑（英語：NMDA receptor modulator）
法律規範狀態
法律規範	美：Investigational New Drug;
識別資訊
	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號	1421866-48-9
PubChem CID	71249967;
ChemSpider	52085607;
UNII	TTT1F11FZB;
KEGG	D11299;
ChEMBL	ChEMBL3545230;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID101031863 ;
化學資訊
化學式	C25H37N5O6
摩爾質量	503.60 g·mol−1
3D模型（JSmol（英語：JSmol））	交互式圖像;
	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；開發代號：GATE-202、NRX-1074、AGN-241660）是一種正在研究的抗抑鬱藥，可作為NMDA受體的新型選擇性調節劑。^[1]^[2]^[3]^[4]目前，Gate Neurosciences正在開發該藥物，用於重度抑鬱症的急性治療。該藥物此前由此前Naurex和艾爾建開發。^[5]^[6]^[7]截至2015年2月，阿匹替奈的靜脈製劑已完成針對重度抑鬱症的IIa期臨床試驗。^[5]^[8]

與雷帕替奈（GLYX-13）類似，其作用機制通過NMDA受體上的獨特結合位點（獨立於甘氨酸位點）發揮作用，以調節受體活性並增強NMDA受體介導的突觸可塑性。^[9]然而，阿匹替奈的體外效力是雷帕替奈的1000倍，因此它可以作為雷帕替奈的改進型後續藥物。^[2]^[5]與雷帕替奈相似，阿匹替奈是一種醯胺化四肽，但通過添加苄基基團進行了結構修飾（英語：Molecular modification），以增強其代謝穩定性和藥代動力學特徵。該藥物在抑鬱症的臨床前模型中顯示出快速而有效的抗抑鬱作用。^[5]此外，阿匹替奈具有良好的耐受性，並且缺乏NMDA受體拮抗劑（如氯胺酮）的分裂樣擬精神病（英語：Psychotomimetism）作用。^[5]

參見

澤奎替奈

參考資料

^ 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. （原始內容存檔於14 July 2014）.
^ Allergan Successfully Completes Naurex Acquisition. Allergan plc (新聞稿). PR Newswire. [2016-11-20].
^ Home - Gate Neurosciences. [2022-05-12] （美國英語）.
^ 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.

外部連結

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. （原始內容存檔於14 July 2014）.

[6] Allergan Successfully Completes Naurex Acquisition. Allergan plc (新聞稿). PR Newswire. [2016-11-20].

[7] Home - Gate Neurosciences. [2022-05-12] （美國英語）.

[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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