右啡烷

右啡烷
臨床資料
其他名稱	DXO, Dextrorphanol
ATC碼	未分配;
法律規範狀態
法律規範	美：Unscheduled;
識別資訊
	IUPAC命名法 (+)-17-methyl-9a,13a,14a-morphinan-3-ol; ;
CAS號	125-73-5
PubChem CID	5360697;
ChemSpider	10489895 ;
UNII	04B7QNO9WS;
ChEMBL	ChEMBL1254766 ;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID301014178 ;
ECHA InfoCard	100.004.323
化學資訊
化學式	C17H23NO
摩爾質量	257.38 g·mol−1
3D模型（JSmol（英語：JSmol））	交互式圖像;
	SMILES CN1CC[C@@]23CCCC[C@@H]2[C@@H]1Cc4c3cc(O)cc4;
	InChI 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 ; Key:JAQUASYNZVUNQP-PVAVHDDUSA-N ;

右啡烷（Dextrorphan，DXO）是一種嗎啡類的精神藥物，具有鎮咳與止咳，或作為解離性致幻劑的作用，也是外消旋嗎汎（英語：Racemorphan）的右旋對映體，另一個左旋對映體則是左旋嗎汎（英語：Levorphanol）。右啡烷是右美沙芬由CYP2D6酶經O-脫甲基（O-demethylated）而生成的，作為一種NMDA拮抗劑，右啡烷可產生右美沙芬所帶來的精神效應。^[2]

藥理學

藥效學

右啡烷^[3]^[4]^[5]^[6]
位置	K_i (nM)	對象	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]
DAT	>1,000	鼠	^[4]
5-HT_1A	>1,000	鼠	^[4]
5-HT_1B_/_1D	54% at 1 μM	鼠	^[4]
5-HT_2A	>1,000	鼠	^[4]
α₁	>1,000	鼠	^[4]
α₂	>1,000	鼠	^[4]
β	35% at 1 μM	鼠	^[4]
D₂	>1,000	鼠	^[4]
H₁	95% at 1 μM	鼠	^[4]
mAChRs	100% at 1 μM	鼠	^[4]
nAChRs	1,300–29,600 (IC₅₀)	鼠	^[4]
VDSCs	ND	ND	ND
除非另加說明，否則以上所示數值均為K_i(nM)。數值越小，說明藥物與該位點的結合力越強。

右啡烷的藥理作用類似於右美沙芬。不過，右啡烷作為NMDA受體拮抗劑的效力要強得多，作為SRI的活性也低得多。不過右啡烷仍保留了右美沙芬作為NRIs時的活性。^[8]並且其對阿片受體的親和力也較右美沙芬強，且高劑量下更強。

藥代動力學

右啡烷的生物半衰期長於其母體化合物，因此在重複服用正常劑量的右美沙芬製劑後容易在血液中蓄積。其還會被CYP3A4進一步轉化為3-羥基嗎啡喃或被葡萄醣醛酸化（英語：Glucuronidation）。^[9]

研究

右啡烷曾被開發用於治療中風，也已進行了II期臨床試驗，但開發工作已經中止。^[10]

參考文獻

^ Bensinger, Peter. Dextrophan and Nalbuphine; Removal from Schedules (PDF). NARA. October 1, 1976 [June 26, 2023]. （原始內容存檔 (PDF)於2023-06-27）.
^ 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 K_i 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]. （原始內容存檔於2023-01-01）.
^ ^4.00 ^4.01 ^4.02 ^4.03 ^4.04 ^4.05 ^4.06 ^4.07 ^4.08 ^4.09 ^4.10 ^4.11 ^4.12 ^4.13 ^4.14 ^4.15 ^4.16 ^4.17 ^4.18 ^4.19 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.
^ Werling LL, Keller A, Frank JG, Nuwayhid SJ. A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp. Neurol. 2007, 207 (2): 248–57. PMID 17689532. S2CID 38476281. doi:10.1016/j.expneurol.2007.06.013.
^ 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.
^ Yu A, Haining RL. 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?. Drug Metabolism and Disposition. November 2001, 29 (11): 1514–20 [2023-10-01]. PMID 11602530. （原始內容存檔於2020-03-12）.
^ Dextrorphan - AdisInsight. [2023-10-01]. （原始內容存檔於2021-07-05）.

[1] Bensinger, Peter. Dextrophan and Nalbuphine; Removal from Schedules (PDF). NARA. October 1, 1976 [June 26, 2023]. （原始內容存檔 (PDF)於2023-06-27）.

[2] 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.

[PDSP-3] Roth BL, Driscol J. PDSP K_i 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]. （原始內容存檔於2023-01-01）.

[pmid26826604-4] 4.00 ^4.01 ^4.02 ^4.03 ^4.04 ^4.05 ^4.06 ^4.07 ^4.08 ^4.09 ^4.10 ^4.11 ^4.12 ^4.13 ^4.14 ^4.15 ^4.16 ^4.17 ^4.18 ^4.19 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.

[pmid17689532-5] Werling LL, Keller A, Frank JG, Nuwayhid SJ. A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp. Neurol. 2007, 207 (2): 248–57. PMID 17689532. S2CID 38476281. doi:10.1016/j.expneurol.2007.06.013.

[pmid27139517-6] 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  .

[pmid7815359-7] 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.

[8] 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.

[DXMdualprobe-9] Yu A, Haining RL. 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?. Drug Metabolism and Disposition. November 2001, 29 (11): 1514–20 [2023-10-01]. PMID 11602530. （原始內容存檔於2020-03-12）.

[AdisInsight-10] Dextrorphan - AdisInsight. [2023-10-01]. （原始內容存檔於2021-07-05）.

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