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Pathway Description
Tramadol Metabolism Pathway
Homo sapiens
Drug Metabolism Pathway
Tramadol (also named Ultram) is a class of opioid pain medication that used for treating pain. Metabolism of tramadol mainly happened in liver cell. The N-demethylation of tramadol is catalyzed by the cytochrome CYP3A4 and CYP2B6 to form N-Desmethyltramadol, which further metabolized to N,N-Didesmethyltramadol through CYP3A4 and CYP2B6 and to N,O-Didesmethyltramadol through CYP2D6. The O-demethylation of tramadol is catalyzed by the cytochrome CYP2D6 to form O-Desmethyltramadol, which further metabolized to O-Desmethyltramadol glucuronide through UDP-glucuronosyltransferase 2B7 and UDP-glucuronosyltransferase 1-8. O-Desmethyltramadol can also be metabolized to N,O-Didesmethyltramadol through CYP2D6.
References
Tramadol Pathway References
[PharmgKB](http://www.pharmgkb.org/pathway/PA165946349)
Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL, Jacoby HI, Selve N: Complementary and synergistic antinociceptive interaction between the enantiomers of tramadol. J Pharmacol Exp Ther. 1993 Oct;267(1):331-40.
Pubmed: 8229760
Reimann W, Schneider F: Induction of 5-hydroxytryptamine release by tramadol, fenfluramine and reserpine. Eur J Pharmacol. 1998 May 22;349(2-3):199-203. doi: 10.1016/s0014-2999(98)00195-2.
Pubmed: 9671098
Wilder-Smith CH, Hill L, Spargo K, Kalla A: Treatment of severe pain from osteoarthritis with slow-release tramadol or dihydrocodeine in combination with NSAID's: a randomised study comparing analgesia, antinociception and gastrointestinal effects. Pain. 2001 Mar;91(1-2):23-31. doi: 10.1016/s0304-3959(00)00414-0.
Pubmed: 11240075
Bravo L, Mico JA, Berrocoso E: Discovery and development of tramadol for the treatment of pain. Expert Opin Drug Discov. 2017 Dec;12(12):1281-1291. doi: 10.1080/17460441.2017.1377697. Epub 2017 Sep 17.
Pubmed: 28920461
Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. doi: 10.2165/00003088-200443130-00004.
Pubmed: 15509185
Lai J, Ma SW, Porreca F, Raffa RB: Tramadol, M1 metabolite and enantiomer affinities for cloned human opioid receptors expressed in transfected HN9.10 neuroblastoma cells. Eur J Pharmacol. 1996 Dec 5;316(2-3):369-72. doi: 10.1016/s0014-2999(96)00770-4.
Pubmed: 8982709
Gillen C, Haurand M, Kobelt DJ, Wnendt S: Affinity, potency and efficacy of tramadol and its metabolites at the cloned human mu-opioid receptor. Naunyn Schmiedebergs Arch Pharmacol. 2000 Aug;362(2):116-21. doi: 10.1007/s002100000266.
Pubmed: 10961373
Subrahmanyam V, Renwick AB, Walters DG, Young PJ, Price RJ, Tonelli AP, Lake BG: Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes. Drug Metab Dispos. 2001 Aug;29(8):1146-55.
Pubmed: 11454734
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