右啡烷（Dextrorphan，DXO）是一种吗啡类的精神药物，具有镇咳与止咳，或作为解离性致幻剂的作用，也是外消旋吗汎的右旋对映体，另一个左旋对映体则是左旋吗汎。右啡烷是右美沙芬由CYP2D6酶经O-脱甲基（O-demethylated）而生成的，作为一种NMDA拮抗剂，右啡烷可产生右美沙芬所带来的精神效应。[2]
Quick Facts 临床资料, 其他名称 ...
右啡烷 |
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| 其他名称 | DXO, Dextrorphanol |
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| ATC码 | |
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| 法律规范 |
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(+)-17-methyl-9a,13a,14a-morphinan-3-ol
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| CAS号 | 125-73-5  Y |
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| PubChem CID | |
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| ChemSpider | |
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| UNII | |
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| ChEMBL | |
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| CompTox Dashboard (EPA) | |
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| ECHA InfoCard | 100.004.323  |
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| 化学式 | C17H23NO |
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| 摩尔质量 | 257.38 g·mol−1 |
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| 3D模型（JSmol） | |
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CN1CC[C@@]23CCCC[C@@H]2[C@@H]1Cc4c3cc(O)cc4
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InChI=1S/C17H23NO/c1-18-9-8-17-7-3-2-4-14(17)16(18)10-12-5-6-13(19)11-15(12)17/h5-6,11,14,16,19H,2-4,7-10H2,1H3/t14-,16+,17+/m1/s1  NKey:JAQUASYNZVUNQP-PVAVHDDUSA-N N
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More information 位置, Ki (nM) ...
右啡烷[3][4][5][6]
| 位置 |
Ki (nM) |
对象 |
引用
|
NMDAR
(MK-801) |
486–906 |
鼠 |
[4]
|
| σ1 |
118–481 |
鼠 |
[4]
|
| σ2 |
11,325–15,582 |
鼠 |
[4]
|
| MOR |
420
>1,000 |
鼠
人 |
[4][7]
|
| DOR |
34,700 |
鼠 |
[4]
|
| KOR |
5,950 |
鼠 |
[4]
|
| SERT |
401–484 |
鼠 |
[4]
|
| NET |
≥340 |
鼠 |
[4]
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| DAT |
>1,000 |
鼠 |
[4]
|
| 5-HT1A |
>1,000 |
鼠 |
[4]
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| 5-HT1B/1D |
54% at 1 μM |
鼠 |
[4]
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| 5-HT2A |
>1,000 |
鼠 |
[4]
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| α1 |
>1,000 |
鼠 |
[4]
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| α2 |
>1,000 |
鼠 |
[4]
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| β |
35% at 1 μM |
鼠 |
[4]
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| D2 |
>1,000 |
鼠 |
[4]
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| H1 |
95% at 1 μM |
鼠 |
[4]
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| mAChRs |
100% at 1 μM |
鼠 |
[4]
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| nAChRs |
1,300–29,600
(IC50) |
鼠 |
[4]
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| VDSCs |
ND |
ND |
ND
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| 除非另加说明，否则以上所示数值均为Ki(nM)。数值越小，说明药物与该位点的结合力越强。
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右啡烷的药理作用类似于右美沙芬。不过，右啡烷作为NMDA受体拮抗剂的效力要强得多，作为SRI的活性也低得多。不过右啡烷仍保留了右美沙芬作为NRIs时的活性。[8]并且其对阿片受体的亲和力也较右美沙芬强，且高剂量下更强。
右啡烷的生物半衰期长于其母体化合物，因此在重复服用正常剂量的右美沙芬制剂后容易在血液中蓄积。其还会被CYP3A4进一步转化为3-羟基吗啡喃或被葡萄糖醛酸化。[9]
右啡烷曾被开发用于治疗中风，也已进行了II期临床试验，但开发工作已经中止。[10]
Zawertailo LA, Kaplan HL, Busto UE, Tyndale RF, Sellers EM. Psychotropic effects of dextromethorphan are altered by the CYP2D6 polymorphism: a pilot study. Journal of Clinical Psychopharmacology. August 1998, 18 (4): 332–337. PMID 9690700. doi:10.1097/00004714-199808000-00014. 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. [14 August 2017]. （原始内容存档于2023-01-01）. Nguyen L, Thomas KL, Lucke-Wold BP, Cavendish JZ, Crowe MS, Matsumoto RR. Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders. Pharmacol. Ther. 2016, 159: 1–22. PMID 26826604. doi:10.1016/j.pharmthera.2016.01.016. Taylor CP, Traynelis SF, Siffert J, Pope LE, Matsumoto RR. Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use. Pharmacol. Ther. 2016, 164: 170–82. PMID 27139517. doi:10.1016/j.pharmthera.2016.04.010 
. Raynor K, Kong H, Mestek A, Bye LS, Tian M, Liu J, Yu L, Reisine T. Characterization of the cloned 人 mu opioid receptor. J. Pharmacol. Exp. Ther. 1995, 272 (1): 423–8. PMID 7815359. Pechnick RN, Poland RE. Comparison of the effects of dextromethorphan, dextrorphan, and levorphanol on the hypothalamo-pituitary-adrenal axis. The Journal of Pharmacology and Experimental Therapeutics. May 2004, 309 (2): 515–522. PMID 14742749. S2CID 274504. doi:10.1124/jpet.103.060038.
