唑吡坦

唑吡坦
臨床資料
懷孕分級	澳: B3 ; ;
給藥途徑	Oral
ATC碼	N05CF02 (WHO) ;
法律規範狀態
法律規範	美：附表IV; UN：《精神藥物公約》附表四; 第二類精神藥品（中國大陸） Class C / POM (UK);
藥物動力學數據
生物利用度	70% (oral) 92% bound in plasma
藥物代謝	肝臟：CYP3A4（~60%）、CYP2C9（~20%）、CYP1A2（~14%）、CYP2D6（<3%）、CYP2C19（<3%）
生物半衰期	2.5至3小時
排泄途徑	56% 經尿液，34% 經糞便
識別資訊
	IUPAC命名法 N,N,6-trimethyl-2-(4-methylphenyl)-; imidazo(1,2-a)pyridine-3-acetamide; ;
CAS號	82626-48-0
PubChem CID	5732;
DrugBank	APRD00095;
ChemSpider	5530;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID7045946 ;
ECHA InfoCard	100.115.604
化學資訊
化學式	C19H21N3O
摩爾質量	307.40 g·mol−1
3D模型（JSmol（英語：JSmol））	交互式圖像;
	SMILES Cc1ccc(cc1)c1nc2ccc(C)cn2c1CC(=O)N(C)C;

唑吡坦（英語：Zolpidem）是一種Z-drugs 安眠藥，約在口服三十分鐘之內起效，藥效維持兩至三小時。市場上常見的藥名包括、Adormix、Ambien、Ambien CR、Edluar、Damixan、Ivedal、Nytamel、Stilnoct、Stilnox、Sucedal、Zoldem、Zolnod及Zolpihexal等^[1]^[2]^[3]^[4]，中國大陸商品名為思諾思（英語：Stilnox），台灣則有佐沛眠（英語：Zolpium）、使蒂諾斯等名稱。

藥理學

唑吡坦是GABA_A受體的正別構調節劑，它選擇性結合GABA_A受體的α1（英語：Gamma-aminobutyric acid receptor subunit alpha-1）亞基，因此它具有較強的催眠和較弱的抗焦慮、肌肉鬆弛和抗驚厥特性。^[5]與地西泮不同，唑吡坦可以與αβGABAA受體結合，它被證明與α1-α1界面結合。^[6]唑吡坦對α2（英語：GABRA2）-和α3（英語：GABRA3）-亞基的親和力比對α₁低10倍，且對含α5（英語：GABRA5）亞基的受體沒有表現出明顯的親和力。^[7]^[8]含α1亞基的苯二氮卓位點（舊稱ω₁）主要存在於大腦中，而含α2亞基的苯二氮卓位點（舊稱ω₂）主要存在於脊柱中，因此唑吡坦更易於與位於大腦而不是脊柱中的GABA_A受體結合。^[9]唑吡坦對含有γ1（英語：GABRG1）和γ3（英語：GABRG3）亞基的受體沒有親和力，並且像絕大多數苯二氮卓類藥物一樣，它也對含有α4（英語：GABRA4）和α6（英語：GABRA6）亞基的受體缺乏親和力。^[10]唑吡坦或許是通過誘導受體構象來調節受體，它誘導的構象能夠通過正調節位點調節激動劑γ-氨基丁酸與其同源受體的結合強度，而不影響脫敏（英語：Downregulation and upregulation）或峰值電流。^[11]

與扎來普隆類似, 唑吡坦可能增加慢波睡眠，但對第二睡眠期沒有影響。^[12]一項比較苯二氮卓類藥物與非苯二氮卓類藥物的文獻綜述顯示，唑吡坦和苯二氮卓類藥物在入睡潛伏期、總睡眠持續時間、覺醒次數、睡眠質量、不良事件、耐受性、失眠反彈和日間警覺性方面幾乎沒有顯著的差異。^[13]

藥代動力學

微粒體研究表明唑吡坦由CYP3A4（61%）、CYP2C9（22%）、CYP1A2（14%）、CYP2D6（<3%）和CYP2C19（<3%）代謝。^[14]只有不到1%以原藥形式從尿液排出。^[5]唑吡坦的絕對生物利用度約為70%，在2小時內達到峰值濃度，在健康成年人中半衰期為2至3小時，^[15]^[5]但在兒童中會縮短，在老年人和肝功能有問題的人群中延長。

在肝功能不全的人群中，其生物利用度增加。消除率減少和消除半衰期增長致大約十個小時。在腎功能不全的人群中，可觀察到清除率中等降低。其他參數不變。唑吡坦不能通過透析清除。^[16]

參考資料

^ Ambien.com. AMBIEN Prescribing Information. Information About a Short-term Treatment for Insomnia - Ambien.com Home Page for Health-care Professionals. Sanofi-Synthelabo Inc. New York, NY 10016. 2004 [2005-06-27]. （原始內容存檔於2005-06-27）.
^ STILNOX (zolpidem tartrate) PRODUCT INFORMATION （頁面存檔備份，存於互聯網檔案館） Sanofi-Synthelabo Australia Pty Limited. April 15, 2004
^ sanofi-aventis : Drugs and Products - CNS - Stilnox/Ambien/Myslee. 2006-11-07 [2006-11-22]. （原始內容存檔於2007-09-27）.
^ Benzodiazepine Names. （原始內容存檔於2008-12-08）.
^ ^5.0 ^5.1 ^5.2 Salvà P, Costa J. Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications. Clinical Pharmacokinetics. September 1995, 29 (3): 142–153. PMID 8521677. S2CID 23391285. doi:10.2165/00003088-199529030-00002.
^ Che Has AT, Absalom N, van Nieuwenhuijzen PS, Clarkson AN, Ahring PK, Chebib M. Zolpidem is a potent stoichiometry-selective modulator of α1β3 GABAA receptors: evidence of a novel benzodiazepine site in the α1-α1 interface. Scientific Reports. June 2016, 6: 28674. Bibcode:2016NatSR...628674C. PMC 4921915 . PMID 27346730. doi:10.1038/srep28674.
^ Pritchett DB, Seeburg PH. Gamma-aminobutyric acidA receptor alpha 5-subunit creates novel type II benzodiazepine receptor pharmacology. Journal of Neurochemistry. May 1990, 54 (5): 1802–4. PMID 2157817. S2CID 86674799. doi:10.1111/j.1471-4159.1990.tb01237.x.
^ Smith AJ, Alder L, Silk J, Adkins C, Fletcher AE, Scales T, Kerby J, Marshall G, Wafford KA, McKernan RM, Atack JR. Effect of alpha subunit on allosteric modulation of ion channel function in stably expressed human recombinant gamma-aminobutyric acid(A) receptors determined using (36)Cl ion flux. Molecular Pharmacology. May 2001, 59 (5): 1108–18. PMID 11306694. S2CID 86156878. doi:10.1124/mol.59.5.1108.
^ Rowlett JK, Woolverton WL. Assessment of benzodiazepine receptor heterogeneity in vivo: apparent pA2 and pKB analyses from behavioral studies. Psychopharmacology. November 1996, 128 (1): 1–16. PMID 8944400. S2CID 25654504. doi:10.1007/s002130050103. （原始內容存檔於12 January 2002）.
^ Wafford KA, Thompson SA, Thomas D, Sikela J, Wilcox AS, Whiting PJ. Functional characterization of human gamma-aminobutyric acidA receptors containing the alpha 4 subunit. Molecular Pharmacology. September 1996, 50 (3): 670–8 [7 October 2007]. PMID 8794909. （原始內容存檔於8 January 2009）.
^ Perrais D, Ropert N. Effect of zolpidem on miniature IPSCs and occupancy of postsynaptic GABAA receptors in central synapses. The Journal of Neuroscience. January 1999, 19 (2): 578–88. PMC 6782193 . PMID 9880578. doi:10.1523/JNEUROSCI.19-02-00578.1999.
^ Noguchi H, Kitazumi K, Mori M, Shiba T. Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats. Journal of Pharmacological Sciences. March 2004, 94 (3): 246–51. PMID 15037809. doi:10.1254/jphs.94.246 . WARNING: The reference indicates that zaleplon-Sonata, not zolpidem, increases Slow-wave sleep
^ Dündar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T. Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis. Human Psychopharmacology. July 2004, 19 (5): 305–22. PMID 15252823. S2CID 10888200. doi:10.1002/hup.594.
^ Von Moltke LL, Greenblatt DJ, Granda BW, Duan SX, Grassi JM, Venkatakrishnan K, et al. Zolpidem metabolism in vitro: responsible cytochromes, chemical inhibitors, and in vivo correlations. British Journal of Clinical Pharmacology. July 1999, 48 (1): 89–97. PMC 2014868 . PMID 10383565. doi:10.1046/j.1365-2125.1999.00953.x.
^ Zolpidem (Monograph). The American Society of Health-System Pharmacists. 27 April 2023 [10 March 2024]. （原始內容存檔於2018-03-16）.
^ 酒石酸唑吡坦说明书 (PDF). [2024-07-07]. （原始內容存檔 (PDF)於2024-07-07）（中文）.

外部連結

Zolpidem. Drug Information Portal. U.S. National Library of Medicine. [2020-10-22]. （原始內容存檔於2020-11-27）.
Man who couldn't talk or move for 8 years 'wakes up' 20 minutes after docs gave him sleeping drug（頁面存檔備份，存於互聯網檔案館）

這是一篇與醫學相關的小作品。您可以透過編輯或修訂擴充其內容。

[1] Ambien.com. AMBIEN Prescribing Information. Information About a Short-term Treatment for Insomnia - Ambien.com Home Page for Health-care Professionals. Sanofi-Synthelabo Inc. New York, NY 10016. 2004 [2005-06-27]. （原始內容存檔於2005-06-27）.

[2] STILNOX (zolpidem tartrate) PRODUCT INFORMATION （頁面存檔備份，存於互聯網檔案館） Sanofi-Synthelabo Australia Pty Limited. April 15, 2004

[3] sanofi-aventis : Drugs and Products - CNS - Stilnox/Ambien/Myslee. 2006-11-07 [2006-11-22]. （原始內容存檔於2007-09-27）.

[4] Benzodiazepine Names. （原始內容存檔於2008-12-08）.

[costahalflife-5] 5.0 ^5.1 ^5.2 Salvà P, Costa J. Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications. Clinical Pharmacokinetics. September 1995, 29 (3): 142–153. PMID 8521677. S2CID 23391285. doi:10.2165/00003088-199529030-00002.

[pmid27346730-6] Che Has AT, Absalom N, van Nieuwenhuijzen PS, Clarkson AN, Ahring PK, Chebib M. Zolpidem is a potent stoichiometry-selective modulator of α1β3 GABAA receptors: evidence of a novel benzodiazepine site in the α1-α1 interface. Scientific Reports. June 2016, 6: 28674. Bibcode:2016NatSR...628674C. PMC 4921915 . PMID 27346730. doi:10.1038/srep28674.

[pmid2157817-7] Pritchett DB, Seeburg PH. Gamma-aminobutyric acidA receptor alpha 5-subunit creates novel type II benzodiazepine receptor pharmacology. Journal of Neurochemistry. May 1990, 54 (5): 1802–4. PMID 2157817. S2CID 86674799. doi:10.1111/j.1471-4159.1990.tb01237.x.

[pmid11306694-8] Smith AJ, Alder L, Silk J, Adkins C, Fletcher AE, Scales T, Kerby J, Marshall G, Wafford KA, McKernan RM, Atack JR. Effect of alpha subunit on allosteric modulation of ion channel function in stably expressed human recombinant gamma-aminobutyric acid(A) receptors determined using (36)Cl ion flux. Molecular Pharmacology. May 2001, 59 (5): 1108–18. PMID 11306694. S2CID 86156878. doi:10.1124/mol.59.5.1108.

[9] Rowlett JK, Woolverton WL. Assessment of benzodiazepine receptor heterogeneity in vivo: apparent pA2 and pKB analyses from behavioral studies. Psychopharmacology. November 1996, 128 (1): 1–16. PMID 8944400. S2CID 25654504. doi:10.1007/s002130050103. （原始內容存檔於12 January 2002）.

[pmid8794909-10] Wafford KA, Thompson SA, Thomas D, Sikela J, Wilcox AS, Whiting PJ. Functional characterization of human gamma-aminobutyric acidA receptors containing the alpha 4 subunit. Molecular Pharmacology. September 1996, 50 (3): 670–8 [7 October 2007]. PMID 8794909. （原始內容存檔於8 January 2009）.

[pmid9880578-11] Perrais D, Ropert N. Effect of zolpidem on miniature IPSCs and occupancy of postsynaptic GABAA receptors in central synapses. The Journal of Neuroscience. January 1999, 19 (2): 578–88. PMC 6782193 . PMID 9880578. doi:10.1523/JNEUROSCI.19-02-00578.1999.

[pmid15037809-12] Noguchi H, Kitazumi K, Mori M, Shiba T. Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats. Journal of Pharmacological Sciences. March 2004, 94 (3): 246–51. PMID 15037809. doi:10.1254/jphs.94.246 . WARNING: The reference indicates that zaleplon-Sonata, not zolpidem, increases Slow-wave sleep

[pmid15252823-13] Dündar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T. Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis. Human Psychopharmacology. July 2004, 19 (5): 305–22. PMID 15252823. S2CID 10888200. doi:10.1002/hup.594.

[micrsome_liver-14] Von Moltke LL, Greenblatt DJ, Granda BW, Duan SX, Grassi JM, Venkatakrishnan K, et al. Zolpidem metabolism in vitro: responsible cytochromes, chemical inhibitors, and in vivo correlations. British Journal of Clinical Pharmacology. July 1999, 48 (1): 89–97. PMC 2014868 . PMID 10383565. doi:10.1046/j.1365-2125.1999.00953.x.

[AHFS2018-15] Zolpidem (Monograph). The American Society of Health-System Pharmacists. 27 April 2023 [10 March 2024]. （原始內容存檔於2018-03-16）.

[16] 酒石酸唑吡坦说明书 (PDF). [2024-07-07]. （原始內容存檔 (PDF)於2024-07-07）（中文）.

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