左旋米那普倫

左旋米那普倫
臨床資料
商品名（英語：Drug nomenclature）	Fetzima
AHFS/Drugs.com	Monograph
給藥途徑	口服 (膠囊劑)
ATC碼	N06AX28 (WHO) ;
法律規範狀態
法律規範	處方藥（℞-only）;
藥物動力學數據
生物利用度	92%
血漿蛋白結合率	22%
藥物代謝	肝（主要是CYP3A4酶）
生物半衰期	12小時
排泄途徑	腎
識別資訊
	IUPAC命名法 (1S,2R)-2-(Aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide; ;
CAS編號	96847-54-0 ; 175131-60-9
PubChem CID	6917779;
IUPHAR/BPS	7435;
DrugBank	DB08918;
ChemSpider	5293005 ;
UNII	UGM0326TXX; HCl: 371U2ZK31U ;
KEGG	D10072 ;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID701025167 ;
化學資訊
化學式	C15H22N2O
莫耳質量	246.35 g·mol−1
3D模型（JSmol（英語：JSmol））	交互式圖像;
	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 ;

左旋米那普倫（商品名：Fetzima），是一種抗抑鬱藥，2013年美國批准該藥用於治療成人重度抑鬱症。這種藥是米那普侖的左旋對映異構物，和米那普侖具有相似的作用和藥理，可作5-羥色胺-去甲腎上腺素再攝取抑制劑（SNRI）。^[4]^[5]

醫療用途

抑鬱症

根據一項為期10周的2期和四項爲期8周3期臨床試驗結果，美國食品藥品監督管理局批准使用左旋米那普侖治療重度抑鬱症。

副作用

在臨床試驗中，左旋米那普侖比安慰劑更常出現這些副作用：噁心、頭暈、出汗、便秘、失眠、心率和血壓升高、尿瀦留、勃起功能障礙和男性射精延遲、嘔吐、心跳過速和心悸。^[6]^[7]

這種藥物對因為勃起功能障礙而導致抑鬱症的患者是把雙面刃^[8]。

藥理

藥物效應動力學

左旋米那普侖和米那普侖相比其他SNRI的不同之處在於它們是更平衡的血清素和去甲腎上腺素再攝取抑制劑。^[9]^[10]^[11]SNRI的血清素對去甲腎上腺素比率如下：文拉法辛=30:1，度洛西汀=10:1，去甲文拉法辛=14:1，米那普侖=1.6:1，左旋米那普侖=0.5:1。^[9]暫時尚不清楚上述比例更平衡的臨床意義，^[9]但可能可提高療效，也可能會增加副作用。^[10]^[11]^[12]

左旋米那普侖可作β位點澱粉樣前體蛋白裂解酶 1（BACE-1）的抑制劑，BACE-1負責β-澱粉樣蛋白斑塊的形成，是治療阿茲海默症的潛在藥物。^[13]

藥物代謝動力學

左旋米那普侖的口服生物利用度為92%，血漿蛋白結合率為22%。^[2]肝臟中的細胞色素P450 酶 CYP3A4負責代謝此物質，^[3]令藥物易受葡萄柚-藥物相互作用影響。該藥物的生物半衰期約為12小時，可每日服藥一次。^[3]左旋米那普侖隨尿液排出。^[3]

歷史

森林實驗室和Pierre Fabre Group開發此藥，2013年7月取得美國食品藥品監督管理局批准使用。^[6]

參考文獻

^ 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]. （原始內容存檔於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]. （原始內容存檔於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]. （原始內容存檔於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.

外部連結

維基共享資源上的相關多媒體資源：左旋米那普倫
Levomilnacipran. Drug Information Portal. U.S. National Library of Medicine. [2022-03-19]. （原始內容存檔於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]. （原始內容存檔於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]. （原始內容存檔於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]. （原始內容存檔於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.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]