查看“右美沙芬”的源代码

{{Drugbox
| image = 右美沙芬化学结构.png

<!-- 化学数据 -->
| C = 18 | H = 25 | N = 1 | O = 1

<!-- 识别信息 -->
| IUPAC_name = (4b<i>S</i>,8a<i>R</i>,9<i>S</i>)-3-Methoxy-11-methyl-6,7,8,8a,9,10-hexahydro-5H-9,4b-(epiminoethano)phenanthrene
| CAS_number = 125-71-3

}}

'''右美沙芬'''（英文：Dextromethorphan），又名右甲吗喃，英文简称DM或DXM，是一种[[处方]]<ref name="Rx-upgrade"></ref>中枢性止咳药，它的氢溴酸盐（Dextromethorphan hydrobromide）常用于药品中，也就是常见的氢溴酸右美沙芬片或氢溴酸右美沙芬糖浆。主要用于[[干咳]]而[[湿咳]]应慎用，通过抑制[[延髓]][[咳嗽中枢]]而发挥中枢性镇咳作用。

== 药品说明书 ==
右美沙芬片每片15mg，成人口服一次1～2片，一日3～4次。哮喘、痰多、肝肾功能不全患者及孕妇慎用。医疗剂量下可见头晕、头痛、嗜睡、易激动、嗳气、食欲缺乏、便秘、恶心、皮肤过敏等副作用，过量时可见神志不清、幻觉、支气管痉挛、呼吸抑制。<ref>{{cite web |url=https://ypk.familydoctor.com.cn/39956/instructions/ |title=右美沙芬片(氢溴酸右美沙芬片) |language=中文 |accessdate=2024-01-04 }}</ref>

== 药理学 ==
=== 药效学 ===
{| class="wikitable sortable floatright" style="font-size:small;"
|+ 右美沙芬及其代谢物结合的受体<ref name="PDSP">{{cite web | title = PDSP K<sub>i</sub> Database | work = Psychoactive Drug Screening Program (PDSP)|author1-link=Bryan Roth | vauthors = Roth BL, Driscol J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=dextromethorphan&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}</ref><ref name="NguyenThomas2016">{{cite journal | vauthors = Nguyen L, Thomas KL, Lucke-Wold BP, Cavendish JZ, Crowe MS, Matsumoto RR | title = Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders | journal = Pharmacology & Therapeutics | volume = 159 | pages = 1–22 | date = March 2016 | pmid = 26826604 | doi = 10.1016/j.pharmthera.2016.01.016 }}</ref><ref name="pmid17689532">{{cite journal | vauthors = Werling LL, Keller A, Frank JG, Nuwayhid SJ | title = A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder | journal = Experimental Neurology | volume = 207 | issue = 2 | pages = 248–257 | date = October 2007 | pmid = 17689532 | doi = 10.1016/j.expneurol.2007.06.013 | s2cid = 38476281 }}</ref><ref name="pmid27139517">{{cite journal | vauthors = Taylor CP, Traynelis SF, Siffert J, Pope LE, Matsumoto RR | title = Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use | journal = Pharmacology & Therapeutics | volume = 164 | pages = 170–182 | date = August 2016 | pmid = 27139517 | doi = 10.1016/j.pharmthera.2016.04.010 | doi-access = free }}</ref>
|-
! 位点 !! {{abbr|DXM|右美沙芬}} !! {{abbrlink|DXO|右啡烷}} !! 来源 !! 参考
|-
| [[NMDA受体|{{abbr|NMDAR|N-甲基-D-天冬氨酸受体}}<br/>(MK-801)]] || 2,120–8,945 || 486–906 || 鼠 || <ref name="NguyenThomas2016"/>
|-
| [[σ-1受体|σ<sub>1</sub>]] || 142–652 || 118–481 || 老鼠 || <ref name="NguyenThomas2016"/>
|-
| [[σ-2受体|σ<sub>2</sub>]] || 11,060–22,864 || 11,325–15,582 || 鼠 || <ref name="NguyenThomas2016"/>
|-
| {{abbrlink|MOR|μ-阿片受体}} || 1,280<br />{{abbr|ND|No data}} || 420<br />&gt;1,000 || 鼠<br/>人类|| <ref name="NguyenThomas2016"/><br /><ref name="pmid7815359">{{cite journal | vauthors = Raynor K, Kong H, Mestek A, Bye LS, Tian M, Liu J, Yu L, Reisine T | display-authors = 6 | title = Characterization of the cloned human mu opioid receptor | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 272 | issue = 1 | pages = 423–428 | date = January 1995 | pmid = 7815359 }}</ref>
|-
| {{abbrlink|DOR|δ-阿片受体}} || 11,500 || 34,700 || 鼠 || <ref name="NguyenThomas2016"/>
|-
| {{abbrlink|KOR|κ-阿片受体}} || 7,000 || 5,950 || 鼠 || <ref name="NguyenThomas2016"/>
|-
| {{abbrlink|SERT|血清素转运体}} || 23–40 || 401–484 || 鼠 || <ref name="NguyenThomas2016"/>
|-
| {{abbrlink|NET|去甲肾上腺素转运体}} || ≥240 || ≥340 || 鼠 || <ref name="NguyenThomas2016"/>
|-
| {{abbrlink|DAT|多巴胺转运体}} || >1,000 || >1,000 || 鼠 || <ref name="NguyenThomas2016"/>
|-
| [[血清素1A受体|5-HT<sub>1A</sub>]] || >1,000 || >1,000 || 鼠 || <ref name="NguyenThomas2016"/>
|-
| [[血清素1B受体|5-HT<sub>1B</sub>]]<sub>/</sub>[[5-HT1D receptor|<sub>1D</sub>]] || 61% at 1&nbsp;μM || 54% at 1&nbsp;μM || 鼠 || <ref name="NguyenThomas2016"/>
|-
| [[血清素2A受体|5-HT<sub>2A</sub>]] || >1,000 || >1,000 || 鼠 || <ref name="NguyenThomas2016"/>
|-
| [[α-1肾上腺素能受体|α<sub>1</sub>]] || >1,000 || >1,000 || 鼠 || <ref name="NguyenThomas2016"/>
|-
| [[α-2肾上腺素能受体|α<sub>2</sub>]] || 60% at 1&nbsp;μM || >1,000 || 鼠 || <ref name="NguyenThomas2016"/>
|-
| [[β-肾上腺素能受体|β]] || >1,000 || 35% at 1&nbsp;μM || 鼠 || <ref name="NguyenThomas2016"/>
|-
| [[多巴胺D2受体|D<sub>2</sub>]] || >1,000 || >1,000 || 鼠 || <ref name="NguyenThomas2016"/>
|-
| [[组胺H1受体|H<sub>1</sub>]] || >1,000 || 95% at 1&nbsp;μM || 鼠 || <ref name="NguyenThomas2016"/>
|-
| {{abbrlink|mAChRs|毒蕈碱乙酰胆碱受体}} || >1,000 || 100% at 1&nbsp;μM || 鼠 || <ref name="NguyenThomas2016"/>
|-
| {{abbrlink|nAChRs|烟碱乙酰胆碱受体}} || 700–8,900<br />([[IC50|IC<sub>50</sub>]]) || 1,300–29,600<br />(IC<sub>50</sub>) || 鼠 || <ref name="NguyenThomas2016"/>
|-
| {{abbrlink|VDSCs|电压依赖性钠通道}} || >50,000 (IC<sub>50</sub>) || {{abbr|ND|No data}} || 鼠 || <ref name="pmid17346698">{{cite journal | vauthors = Lee JH, Shin EJ, Jeong SM, Lee BH, Yoon IS, Lee JH, Choi SH, Kim YH, Pyo MK, Lee SM, Chae JS, Rhim H, Oh JW, Kim HC, Nah SY | display-authors = 6 | title = Effects of dextrorotatory morphinans on brain Na+ channels expressed in Xenopus oocytes | journal = European Journal of Pharmacology | volume = 564 | issue = 1–3 | pages = 7–17 | date = June 2007 | pmid = 17346698 | doi = 10.1016/j.ejphar.2007.01.088 }}</ref><ref name="pmid23139844">{{cite journal | vauthors = Gao XF, Yao JJ, He YL, Hu C, Mei YA | title = Sigma-1 receptor agonists directly inhibit Nav1.2/1.4 channels | journal = PLOS ONE | volume = 7 | issue = 11 | pages = e49384 | year = 2012 | pmid = 23139844 | pmc = 3489664 | doi = 10.1371/journal.pone.0049384 | doi-access = free | bibcode = 2012PLoSO...749384G }}</ref>
|- class="sortbottom"
| colspan="5" style="width: 1px;" | 除非另有说明，数值均为 K<sub>i</sub>(nM)。该值越小则药物与该位点的结合越强。
|}

右美沙芬通过[[MK-801]]/[[PCP]]位点非竞争性拮抗[[NMDA受体]]。<ref name="pmid24648790">{{cite journal | vauthors = Burns JM, Boyer EW | title = Antitussives and substance abuse | journal = Substance Abuse and Rehabilitation | volume = 4 | pages = 75–82 | year = 2013 | pmid = 24648790 | pmc = 3931656 | doi = 10.2147/SAR.S36761 | doi-access = free }}</ref>它还是血清素和去甲肾上腺素转运体抑制剂（SNRI）；是σ-1受体的激动剂；是[[烟碱乙酰胆碱受体]]的[[负变构调节剂]]；右美沙芬还是[[血清素]][[5HT1B|1B]]/[[5HT1D|1D]]、[[组胺H1]]、α2-肾上腺素能和[[毒蕈碱乙酰胆碱受体]]的[[配体]]。<ref name="NguyenThomas2016"/><ref name="pmid24648790" />

右美沙芬的代谢物之一[[右啡烷]]作为比右美沙芬更强的NMDA拮抗剂，通常比右美沙芬更造成[[解离]]。<ref name="pmid10064839">{{cite journal | vauthors = Chou YC, Liao JF, Chang WY, Lin MF, Chen CF | title = Binding of dimemorfan to sigma-1 receptor and its anticonvulsant and locomotor effects in mice, compared with dextromethorphan and dextrorphan | journal = Brain Research | volume = 821 | issue = 2 | pages = 516–519 | date = March 1999 | pmid = 10064839 | doi = 10.1016/S0006-8993(99)01125-7 | s2cid = 22762264 }}</ref>而右美沙芬的另一种主要代谢物(+)-3-甲氧基吗啡喃的作用尚不完全明确。<ref>{{cite journal | vauthors = Schmider J, Greenblatt DJ, Fogelman SM, von Moltke LL, Shader RI | title = Metabolism of dextromethorphan in vitro: involvement of cytochromes P450 2D6 and 3A3/4, with a possible role of 2E1 | journal = Biopharmaceutics & Drug Disposition | volume = 18 | issue = 3 | pages = 227–240 | date = April 1997 | pmid = 9113345 | doi = 10.1002/(SICI)1099-081X(199704)18:3<227::AID-BDD18>3.0.CO;2-L | s2cid = 5638973 }}</ref>

=== 药代动力学 ===
右美沙芬在口服后大约15~30分钟内开始起效，在2~3小时达到[[血药峰值]]，它的生物半衰期在代谢能力强的人身上大约为2~4小时，而代谢能力弱的人有可能到达24小时，大部分通过尿液排出。<ref name = MSR>{{cite web|title=Balminil DM, Benylin DM (dextromethorphan) dosing, indications, interactions, adverse effects, and more|work=Medscape Reference|publisher=WebMD|accessdate=2024-02-11|url=http://reference.medscape.com/drug/balminil-dm-benylin-dm-dextromethorphan-343401#showall|archive-date=2019-03-31|archive-url=https://web.archive.org/web/20190331154154/https://reference.medscape.com/drug/balminil-dm-benylin-dm-dextromethorphan-343401#showall|dead-url=no}}</ref>

右美沙芬口服时经过首过效应让部分药物通过O-去甲基化代谢成右美沙芬的活性代谢产物右啡烷，同时通过N-去甲基化生成3-甲氧基吗啡喃（MEM），<ref name="DXMdualprobe">{{cite journal | vauthors = Yu A, Haining RL | title = Comparative contribution to dextromethorphan metabolism by cytochrome P450 isoforms in vitro: can dextromethorphan be used as a dual probe for both CTP2D6 and CYP3A activities? | journal = Drug Metabolism and Disposition | volume = 29 | issue = 11 | pages = 1514–1520 | date = November 2001 | pmid = 11602530 | url = http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11602530 | access-date = 2015-04-26 | archive-date = 2020-03-12 | archive-url = https://web.archive.org/web/20200312134718/http://dmd.aspetjournals.org/content/29/11/1514.long | url-status = dead }}</ref><ref name="nhtsa">{{cite web|url=http://www.nhtsa.dot.gov/PEOPLE/injury/research/job185drugs/dextromethorphan.htm|title=Dextromethorphan|work=National Highway Traffic Safety Administration (NHTSA)|archive-url=https://web.archive.org/web/20080801054711/http://www.nhtsa.dot.gov/PEOPLE/injury/research/job185drugs/dextromethorphan.htm|archive-date=2008-08-01}}</ref>并与葡萄糖醛酸和硫酸根离子部分结合。右美沙芬最主要的代谢产物是右啡烷，其中80%的右啡烷是由CYP2D6产生的，在CYP2D6酶活性较差的人身上可能会使AUC增加150倍、中位半衰期延长至6~8倍。<ref name="pmid8841152">{{cite journal | vauthors = Capon DA, Bochner F, Kerry N, Mikus G, Danz C, Somogyi AA | title = The influence of CYP2D6 polymorphism and quinidine on the disposition and antitussive effect of dextromethorphan in humans | journal = Clinical Pharmacology and Therapeutics | volume = 60 | issue = 3 | pages = 295–307 | date = September 1996 | pmid = 8841152 | doi = 10.1016/S0009-9236(96)90056-9 | s2cid = 10147669 }}</ref>右美沙芬的代谢产物之一3-甲氧基吗啡喃约90%都是通过CYP3A4的N-去甲基化产生的。<ref name="pmid8841152"></ref>

== 药物滥用 ==
右美沙芬时常被滥用，其中属未成年中较为流行。<ref>{{cite web |url=https://new.qq.com/rain/a/20221229A04TJH00 |title=右美沙芬滥用者的隐秘世界 |publisher=苏子涵 、李沁桦、刘汨 |date=2022-12-29 |accessdate=2024-02-11 }}</ref>由于其被滥用的潜质，中国国家药监局在2021年12月16日将右美沙芬口服单方制从[[非处方药]]剂转换为[[处方药]]并随后实行[[网络禁售]]。<ref name="Rx-upgrade">{{cite news |title=国家药监局关于氢溴酸右美沙芬口服单方制剂转换为处方药的公告（2021年第151号） |url=https://www.nmpa.gov.cn/directory/web/nmpa/yaopin/ypggtg/20211227162159192.html |accessdate=2024-02-11 |publisher=国家药品监督管理局 |date=2021-12-16 |archive-date=2022-02-15 |archive-url=https://web.archive.org/web/20220215013414/https://www.nmpa.gov.cn/directory/web/nmpa/xxgk/ggtg/qtggtg/20211227162159192.html |dead-url=no }}</ref><ref>{{cite web |url=https://www.nmpa.gov.cn/yaopin/ypggtg/20221130200847133.html |title=国家药监局关于发布药品网络销售禁止清单（第一版）的公告（2022年 第111号） |publisher=国家药品监督管理局 |date=2022-11-30 |accessdate=2024-02-11 }}</ref>，并在2024年5月将其进一步加入精神药品目录（7月起实行），但右美沙芬至今仍能在药店随意购买。<ref>{{cite web |url=http://opinion.people.com.cn/n1/2023/1205/c436867-40132522.html |title=人民热评：右美沙芬被滥用，谁在顶风作案？ |publisher=人民网-观点频道 |date=2023-12-05 |accessdate=2024-02-11 }}</ref>

== 法律地位 ==
=== 中国 ===
中国大陆在2021年将右美沙芬从非处方药改为处方药，<ref name="Rx-upgrade"></ref>随后又在2024年列入[[精神药品品种目]]第二类。<ref>{{cite web |url=https://www.nmpa.gov.cn/xxgk/ggtg/ypggtg/ypqtggtg/20240507084000186.html |title=国家药监局 公安部 国家卫生健康委关于调整精神药品目录的公告（2024年第54号） |date=2024-05-07 |accessdate=2024-05-07 }}</ref>

== 参考文献 ==
{{Reflist}}