右美沙芬
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，通过抑制延髓咳嗽中枢而发挥中枢性镇咳作用。
| 文件:右美沙芬化学结构.png | |
| 化学数据 | |
|---|---|
| 化学式 | C18H25NO |
| 摩尔质量 | 271.40 g·mol−1 |
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。[1]
药理学
| 点位 | DXM | DXO | 来源 | 参考 |
|---|---|---|---|---|
| NMDAR (MK-801) |
2,120–8,945 | 486–906 | 鼠 | [3] |
| σ1 | 142–652 | 118–481 | 老鼠 | [3] |
| σ2 | 11,060–22,864 | 11,325–15,582 | 鼠 | [3] |
| MOR | 1,280 ND |
420 >1,000 |
鼠 人类 |
[3] [6] |
| DOR | 11,500 | 34,700 | 鼠 | [3] |
| KOR | 7,000 | 5,950 | 鼠 | [3] |
| SERT | 23–40 | 401–484 | 鼠 | [3] |
| NET | ≥240 | ≥340 | 鼠 | [3] |
| DAT | >1,000 | >1,000 | 鼠 | [3] |
| 5-HT1A | >1,000 | >1,000 | 鼠 | [3] |
| 5-HT1B/1D | 61% at 1 μM | 54% at 1 μM | 鼠 | [3] |
| 5-HT2A | >1,000 | >1,000 | 鼠 | [3] |
| α1 | >1,000 | >1,000 | 鼠 | [3] |
| α2 | 60% at 1 μM | >1,000 | 鼠 | [3] |
| β | >1,000 | 35% at 1 μM | 鼠 | [3] |
| D2 | >1,000 | >1,000 | 鼠 | [3] |
| H1 | >1,000 | 95% at 1 μM | 鼠 | [3] |
| mAChRs | >1,000 | 100% at 1 μM | 鼠 | [3] |
| nAChRs | 700–8,900 (IC50) |
1,300–29,600 (IC50) |
鼠 | [3] |
| VDSCs | >50,000 (IC50) | ND | 鼠 | [7][8] |
| 除非另有说明，数值均为 Ki(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。[9]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1B/1D、组胺H1、α2-肾上腺素能和毒蕈碱乙酰胆碱受体的配体。[3][9]
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。[10]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。[11]
参考文献
- ↑ "右美沙芬片(氢溴酸右美沙芬片)" (in 中文). Retrieved 2024-01-04.
- ↑ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 Nguyen L, Thomas KL, Lucke-Wold BP, Cavendish JZ, Crowe MS, Matsumoto RR (March 2016). "Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders". Pharmacology & Therapeutics. 159: 1–22. doi:10.1016/j.pharmthera.2016.01.016. PMID 26826604.
- ↑ Werling LL, Keller A, Frank JG, Nuwayhid SJ (October 2007). "A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder". Experimental Neurology. 207 (2): 248–257. doi:10.1016/j.expneurol.2007.06.013. PMID 17689532. S2CID 38476281.
- ↑ Taylor CP, Traynelis SF, Siffert J, Pope LE, Matsumoto RR (August 2016). "Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use". Pharmacology & Therapeutics. 164: 170–182. doi:10.1016/j.pharmthera.2016.04.010. PMID 27139517.
- ↑ Raynor K, Kong H, Mestek A, Bye LS, Tian M, Liu J, et al. (January 1995). "Characterization of the cloned human mu opioid receptor". The Journal of Pharmacology and Experimental Therapeutics. 272 (1): 423–428. PMID 7815359.
- ↑ Lee JH, Shin EJ, Jeong SM, Lee BH, Yoon IS, Lee JH, et al. (June 2007). "Effects of dextrorotatory morphinans on brain Na+ channels expressed in Xenopus oocytes". European Journal of Pharmacology. 564 (1–3): 7–17. doi:10.1016/j.ejphar.2007.01.088. PMID 17346698.
- ↑ Gao XF, Yao JJ, He YL, Hu C, Mei YA (2012). "Sigma-1 receptor agonists directly inhibit Nav1.2/1.4 channels". PLOS ONE. 7 (11): e49384. Bibcode:2012PLoSO...749384G. doi:10.1371/journal.pone.0049384. PMC 3489664. PMID 23139844.
- ↑ 9.0 9.1 Burns JM, Boyer EW (2013). "Antitussives and substance abuse". Substance Abuse and Rehabilitation. 4: 75–82. doi:10.2147/SAR.S36761. PMC 3931656. PMID 24648790.
- ↑ Chou YC, Liao JF, Chang WY, Lin MF, Chen CF (March 1999). "Binding of dimemorfan to sigma-1 receptor and its anticonvulsant and locomotor effects in mice, compared with dextromethorphan and dextrorphan". Brain Research. 821 (2): 516–519. doi:10.1016/S0006-8993(99)01125-7. PMID 10064839. S2CID 22762264.
- ↑ Schmider J, Greenblatt DJ, Fogelman SM, von Moltke LL, Shader RI (April 1997). "Metabolism of dextromethorphan in vitro: involvement of cytochromes P450 2D6 and 3A3/4, with a possible role of 2E1". Biopharmaceutics & Drug Disposition. 18 (3): 227–240. doi:10.1002/(SICI)1099-081X(199704)18:3<227::AID-BDD18>3.0.CO;2-L. PMID 9113345. S2CID 5638973.