右啡烷

化合物

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]

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
  • Unscheduled[1]
識別資訊
  • (+)-17-methyl-9a,13a,14a-morphinan-3-ol
CAS號125-73-5  checkY
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard英語CompTox Chemicals Dashboard (EPA)
ECHA InfoCard100.004.323 編輯維基數據鏈接
化學資訊
化學式C17H23NO
摩爾質量257.38 g·mol−1
3D模型(JSmol英語JSmol
  • CN1CC[C@@]23CCCC[C@@H]2[C@@H]1Cc4c3cc(O)cc4
  • 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 ☒N
  • Key:JAQUASYNZVUNQP-PVAVHDDUSA-N ☒N

藥理學

藥效學

右啡烷[3][4][5][6]
位置 Ki (nM) 對象 引用
NMDAR
(MK-801)
486–906 [4]
σ1 118–481 [4]
σ2 11,325–15,582 [4]
MOR 420
>1,000

[4][7]
DOR 34,700 [4]
KOR 5,950 [4]
SERT 401–484 [4]
NET ≥340 [4]
DAT >1,000 [4]
5-HT1A >1,000 [4]
5-HT1B/1D 54% at 1 μM [4]
5-HT2A >1,000 [4]
α1 >1,000 [4]
α2 >1,000 [4]
β 35% at 1 μM [4]
D2 >1,000 [4]
H1 95% at 1 μM [4]
mAChRs 100% at 1 μM [4]
nAChRs 1,300–29,600
(IC50)
[4]
VDSCs ND ND ND
除非另加說明,否則以上所示數值均為Ki(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

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