左旋米那普伦

左旋米那普伦
临床资料
商品名（英语：Drug nomenclature）	Fetzima
AHFS/Drugs.com	Monograph
给药途径	口服 (胶囊剂)
ATC码	N06AX28 (WHO) ;
法律规范状态
法律规范	处方药（℞-only）;
药物动力学数据
生物利用度	92%
血浆蛋白结合率	22%
药物代谢	肝（主要是CYP3A4酶）
生物半衰期	12小时
排泄途径	肾
识别信息
	IUPAC命名法 (1S,2R)-2-(Aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide; ;
CAS号	96847-54-0 ; 175131-60-9
PubChem CID	6917779;
IUPHAR/BPS	7435;
DrugBank	DB08918;
ChemSpider	5293005 ;
UNII	UGM0326TXX; HCl: 371U2ZK31U ;
KEGG	D10072 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID701025167 ;
化学信息
化学式	C15H22N2O
摩尔质量	246.35 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES CCN(CC)C(=O)[C@]1(C[C@H]1CN)C2=CC=CC=C2;
	InChI InChI=1S/C15H22N2O/c1-3-17(4-2)14(18)15(10-13(15)11-16)12-8-6-5-7-9-12/h5-9,13H,3-4,10-11,16H2,1-2H3/t13-,15+/m0/s1 ; Key:GJJFMKBJSRMPLA-DZGCQCFKSA-N ;

左旋米那普伦（商品名：Fetzima），是一种抗抑郁药，2013年美国批准该药用于治疗成人重度抑郁症。这种药是米那普仑的左旋对映异构体，和米那普仑具有相似的作用和药理，可作5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRI）。^[4]^[5]

医疗用途

一瓶Fetzima

抑郁症

根据一项为期10周的2期和四项为期8周3期临床试验结果，美国食品药品监督管理局批准使用左旋米那普仑治疗重度抑郁症。

副作用

在临床试验中，左旋米那普仑比安慰剂更常出现这些副作用：恶心、头晕、出汗、便秘、失眠、心率和血压升高、尿潴留、勃起功能障碍和男性射精延迟、呕吐、心跳过速和心悸。^[6]^[7]

这种药物对因为勃起功能障碍而导致抑郁症的患者是把双面刃^[8]。

药理

药物效应动力学

左旋米那普仑和米那普仑相比其他SNRI的不同之处在于它们是更平衡的血清素和去甲肾上腺素再摄取抑制剂。^[9]^[10]^[11]SNRI的血清素对去甲肾上腺素比率如下：文拉法辛=30:1，度洛西汀=10:1，去甲文拉法辛=14:1，米那普仑=1.6:1，左旋米那普仑=0.5:1。^[9]暂时尚不清楚上述比例更平衡的临床意义，^[9]但可能可提高疗效，也可能会增加副作用。^[10]^[11]^[12]

左旋米那普仑可作β位点淀粉样前体蛋白裂解酶 1（BACE-1）的抑制剂，BACE-1负责β-淀粉样蛋白斑块的形成，是治疗阿尔茨海默病的潜在药物。^[13]

药物代谢动力学

左旋米那普仑的口服生物利用度为92%，血浆蛋白结合率为22%。^[2]肝脏中的细胞色素P450 酶 CYP3A4负责代谢此物质，^[3]令药物易受葡萄柚-药物相互作用影响。该药物的生物半衰期约为12小时，可每日服药一次。^[3]左旋米那普仑随尿液排出。^[3]

历史

森林实验室和Pierre Fabre Group开发此药，2013年7月取得美国食品药品监督管理局批准使用。^[6]

参考文献

^ Fetzima (levomilnacipran) Extended-Release Capsules, for Oral Use. Full Prescribing Information. Forest Pharmaceuticals, Inc. Subsidiary of Forest Laboratories, Inc. St. Louis, MO 63045 USA. July 2014 [2 September 2016]. （原始内容存档于2016-08-17）.
^ ^2.0 ^2.1 Alan F. Schatzberg; Charles B. Nemeroff. The American Psychiatric Association Publishing Textbook of Psychopharmacology. American Psychiatric Pub. 10 May 2017: 533–. ISBN 978-1-61537-122-8.
^ ^3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 Stephen M. Stahl. Prescriber's Guide: Stahl's Essential Psychopharmacology. Cambridge University Press. 31 March 2017: 373–376. ISBN 978-1-108-22874-9.
^ Pierre Fabre Medicament and Forest Laboratories to Collaborate on Development and Commercialization of F2695 for Depression - FierceBiotech. [2022-03-19]. （原始内容存档于2016-03-03）.
^ Which bioequivalence study for a racemic drug? Application to milnacipran. European Journal of Drug Metabolism and Pharmacokinetics. 1998, 23 (2): 166–71. PMID 9725476. doi:10.1007/bf03189334.
^ ^6.0 ^6.1 Citrome L. Levomilnacipran for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant--what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?. Int. J. Clin. Pract. November 2013, 67 (11): 1089–104. PMID 24016209. doi:10.1111/ijcp.12298.
^ A phase III, double-blind, placebo-controlled, flexible-dose study of levomilnacipran extended-release in patients with major depressive disorder. J Clin Psychopharmacol. February 2014, 34 (1): 47–56. PMC 4047313  . PMID 24172209. doi:10.1097/JCP.0000000000000060.
^ 阳痿导致抑郁症抑郁男更易阳痿 - 家庭医生在线男科频道. www.familydoctor.com.cn. [2022-03-24]. （原始内容存档于2022-04-20）.
^ ^9.0 ^9.1 ^9.2 Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison. Innov Clin Neurosci. March 2014, 11 (3–4): 37–42. PMC 4008300  . PMID 24800132.
^ ^10.0 ^10.1 Levomilnacipran (Fetzima): A New Serotonin-Norepinephrine Reuptake Inhibitor for the Treatment of Major Depressive Disorder. J Pharm Pract. December 2013, 27 (4): 389–395. PMID 24381243. doi:10.1177/0897190013516504.
^ ^11.0 ^11.1 Milnacipran: a unique antidepressant?. Neuropsychiatr Dis Treat. 2010, 6: 23–31. PMC 2938282  . PMID 20856597. doi:10.2147/NDT.S11777.
^ Does adding noradrenaline reuptake inhibition to selective serotonin reuptake inhibition improve efficacy in patients with depression? A systematic review of meta-analyses and large randomised pragmatic trials. J. Psychopharmacol. (Oxford). August 2013, 27 (8): 740–58. PMID 23832963. doi:10.1177/0269881113494937.
^ Fetzima (levomilnacipran), a drug for major depressive disorder as a dual inhibitor for human serotonin transporters and beta-site amyloid precursor protein cleaving enzyme-1. CNS Neurol Disord Drug Targets. 2014, 13 (8): 1427–31. PMID 25345508. doi:10.2174/1871527313666141023145703.

外部链接

维基共享资源上的相关多媒体资源：左旋米那普伦
Levomilnacipran. Drug Information Portal. U.S. National Library of Medicine. [2022-03-19]. （原始内容存档于2022-04-20）.

[Fetzima_PI-1] Fetzima (levomilnacipran) Extended-Release Capsules, for Oral Use. Full Prescribing Information. Forest Pharmaceuticals, Inc. Subsidiary of Forest Laboratories, Inc. St. Louis, MO 63045 USA. July 2014 [2 September 2016]. （原始内容存档于2016-08-17）.

[SchatzbergNemeroff2017-2] 2.0 ^2.1 Alan F. Schatzberg; Charles B. Nemeroff. The American Psychiatric Association Publishing Textbook of Psychopharmacology. American Psychiatric Pub. 10 May 2017: 533–. ISBN 978-1-61537-122-8.

[Stahl2017-3] 3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 Stephen M. Stahl. Prescriber's Guide: Stahl's Essential Psychopharmacology. Cambridge University Press. 31 March 2017: 373–376. ISBN 978-1-108-22874-9.

[urlPierre_Fabre_Medicament_and_Forest_Laboratories_to_Collaborate_on_Development_and_Commercialization_of_F2695_for_Depression_-_FierceBiotech-4] Pierre Fabre Medicament and Forest Laboratories to Collaborate on Development and Commercialization of F2695 for Depression - FierceBiotech. [2022-03-19]. （原始内容存档于2016-03-03）.

[pmid9725476-5] Which bioequivalence study for a racemic drug? Application to milnacipran. European Journal of Drug Metabolism and Pharmacokinetics. 1998, 23 (2): 166–71. PMID 9725476. doi:10.1007/bf03189334.

[pmid24016209-6] 6.0 ^6.1 Citrome L. Levomilnacipran for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant--what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?. Int. J. Clin. Pract. November 2013, 67 (11): 1089–104. PMID 24016209. doi:10.1111/ijcp.12298.

[pmid24172209-7] A phase III, double-blind, placebo-controlled, flexible-dose study of levomilnacipran extended-release in patients with major depressive disorder. J Clin Psychopharmacol. February 2014, 34 (1): 47–56. PMC 4047313  . PMID 24172209. doi:10.1097/JCP.0000000000000060.

[8] 阳痿导致抑郁症抑郁男更易阳痿 - 家庭医生在线男科频道. www.familydoctor.com.cn. [2022-03-24]. （原始内容存档于2022-04-20）.

[pmid24800132-9] 9.0 ^9.1 ^9.2 Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison. Innov Clin Neurosci. March 2014, 11 (3–4): 37–42. PMC 4008300  . PMID 24800132.

[pmid24381243-10] 10.0 ^10.1 Levomilnacipran (Fetzima): A New Serotonin-Norepinephrine Reuptake Inhibitor for the Treatment of Major Depressive Disorder. J Pharm Pract. December 2013, 27 (4): 389–395. PMID 24381243. doi:10.1177/0897190013516504.

[pmid20856597-11] 11.0 ^11.1 Milnacipran: a unique antidepressant?. Neuropsychiatr Dis Treat. 2010, 6: 23–31. PMC 2938282  . PMID 20856597. doi:10.2147/NDT.S11777.

[pmid23832963-12] Does adding noradrenaline reuptake inhibition to selective serotonin reuptake inhibition improve efficacy in patients with depression? A systematic review of meta-analyses and large randomised pragmatic trials. J. Psychopharmacol. (Oxford). August 2013, 27 (8): 740–58. PMID 23832963. doi:10.1177/0269881113494937.

[pmid25345508-13] Fetzima (levomilnacipran), a drug for major depressive disorder as a dual inhibitor for human serotonin transporters and beta-site amyloid precursor protein cleaving enzyme-1. CNS Neurol Disord Drug Targets. 2014, 13 (8): 1427–31. PMID 25345508. doi:10.2174/1871527313666141023145703.

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