Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR0476)
Drug Name
Dextromethorphan hydrobromide
Synonyms
Dextromethorphan (hydrobromide); Dextromethorphan HBr; Dextromethorphan bromide; Dextromethorphan hydrobromide; Dextromethorphan hydrobromide anhydrous; Dextromethorphan polistirex; Dextrometorphan hydrobromide; Dormethan; EINECS 204-750-1; Medicon; Methorate hydrobromide; Metrorat; Ro 1-5470/5; Romilar; Romilar hydrobromide; Tusilan; Tussade; UNII-Z0CG3115FG; Z0CG3115FG; d-3-Methoxy-N-methylmorphinan hydrobromide; d-Methorphan hydrobromide; Dextromethorphan; Destrometerfano [DCIT]; Dextromethorfan; Dextromethorfan [Czech]; Dextromethorphan [USP:INN:BAN]; Dextromethorphane; Dextromethorphane [INN-French]; Dextromethorphanum; Dextromethorphanum [INN-Latin]; Dextrometorfano; Dextrometorfano [INN-Spanish]; Dextrometorphan; Dextromorphan; HSDB 3056; Hihustan M.; Morphinan, 3-methoxy-17-methyl-, (9alpha,13alpha,14alpha)-; UNII-7355X3ROTS; d-Methorphan; delta-Methorphan; dextromethorphan; 125-71-3; BA 2666; 125-69-9; Antussan; Delsym; Demorphan
Indication Atherosclerosis [ICD11: BA80] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 352.3 Topological Polar Surface Area 12.5
Heavy Atom Count 21 Rotatable Bond Count 1
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 2
Cross-matching ID
PubChem CID
5464025
CAS Number
125-69-9
TTD Drug ID
D09OBB
Formula
C18H26BrNO
Canonical SMILES
CN1CCC23CCCCC2C1CC4=C3C=C(C=C4)OC.Br
InChI
1S/C18H25NO.BrH/c1-19-10-9-18-8-4-3-5-15(18)17(19)11-13-6-7-14(20-2)12-16(13)18;/h6-7,12,15,17H,3-5,8-11H2,1-2H3;1H/t15-,17+,18+;/m1./s1
InChIKey
MISZALMBODQYFT-URVXVIKDSA-N
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
(+)-3-Methoxymorphinan DM000831
660391
Oxidation - N-Demethylation 1 [12] , [13]
Dextrorphan DM000825
5360697
Oxidation - O-Demethylation 1 [12] , [13]
3-hydroxymorphinan DM000826
5463854
Oxidation - O-Demethylation 2 [12]
3-hydroxymorphinan DM000826
5463854
Oxidation - N-Demethylation 2 [14] , [13]
Dextrorphan O-glucuronide DM000830
24883428
Conjugation - Glucuronidation 2 [12] , [15] , [16]
Dextrorphan sulfate DM000829 N. A. Conjugation - Sulfation 2 [14]
3-hydroxymorphinan O-glucuronide DM000828 N. A. Conjugation - Glucuronidation 3 [12] , [13]
3-hydroxymorphinan O-glucuronide DM000828 N. A. Conjugation - Glucuronidation 3 [14] , [13]
3-hydroxymorphinan sulfate DM000827
154699758
Conjugation - Sulfation 3 [14]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR000817 Dextromethorphan hydrobromide Dextrorphan Oxidation - O-Demethylation CYP2C9 ... [12], [13]
MR000818 Dextromethorphan hydrobromide (+)-3-Methoxymorphinan Oxidation - N-Demethylation CYP3A4 ... [12], [13]
MR000816 (+)-3-Methoxymorphinan 3-hydroxymorphinan Oxidation - O-Demethylation CYP2D6 [12]
MR000811 Dextrorphan 3-hydroxymorphinan Oxidation - N-Demethylation CYP3A4 ... [14], [13]
MR000812 Dextrorphan Dextrorphan sulfate Conjugation - Sulfation Unclear [14]
MR000813 Dextrorphan Dextrorphan O-glucuronide Conjugation - Glucuronidation UGT2B4 ... [12], [15], [16]
MR000814 3-hydroxymorphinan 3-hydroxymorphinan sulfate Conjugation - Sulfation Unclear [14]
MR000815 3-hydroxymorphinan 3-hydroxymorphinan O-glucuronide Conjugation - Glucuronidation UGT2B4 ... [12], [13]
⏷ Show the Full List of 8 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cholesterol 24-hydroxylase (CYP46A1) DME0028 Homo sapiens
CP46A_HUMAN
1.14.14.25
[2]
Cytochrome P450 102A1 (cyp102) DME1075 Bacillus megaterium
CPXB_BACMB
1.14.14.1
[3]
Cytochrome P450 130A1 (cyp130) DME1442 Mycobacterium tuberculosis
CP130_MYCTU
1.14.15.29
[4]
Cytochrome P450 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_HUMAN
1.14.14.1
[5]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[6]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[7]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[8]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[9]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[10]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[6]
UDP-glucuronosyltransferase 2B15 (UGT2B15) DME0049 Homo sapiens
UDB15_HUMAN
2.4.1.17
[11]
UDP-glucuronosyltransferase 2B17 (UGT2B17) DME0066 Homo sapiens
UDB17_HUMAN
2.4.1.17
[11]
UDP-glucuronosyltransferase 2B4 (UGT2B4) DME0047 Homo sapiens
UD2B4_HUMAN
2.4.1.17
[11]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DME0040 Homo sapiens
UD2B7_HUMAN
2.4.1.17
[11]
⏷ Show the Full List of 14  DME(s)
References
1 Dextromethorphan Hydrobromide was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Biochemistry. 2003 Dec 9;42(48):14284-92.
3 The bacterial P450 BM3: a prototype for a biocatalyst with human P450 activities. Trends Biotechnol. 2007 Jul;25(7):289-98.
4 Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets? Appl Microbiol Biotechnol. 2019 May;103(9):3597-3614.
5 Enzymes in addition to CYP3A4 and 3A5 mediate N-demethylation of dextromethorphan in human liver microsomes. Biopharm Drug Dispos. 1999 Oct;20(7):341-6.
6 Multiple human cytochromes contribute to biotransformation of dextromethorphan in-vitro: role of CYP2C9, CYP2C19, CYP2D6, and CYP3A. J Pharm Pharmacol. 1998 Sep;50(9):997-1004.
7 Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet. 2009;48(11):689-723.
8 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 Metab Dispos. 2001 Nov;29(11):1514-20.
9 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
10 Characterization of dextromethorphan N-demethylation by human liver microsomes. Contribution of the cytochrome P450 3A (CYP3A) subfamily. Biochem Pharmacol. 1994 Jul 5;48(1):173-82.
11 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development Curr Med Chem. 2009;16(27):3480-675. doi: 10.2174/092986709789057635.
12 LC-MS/MS analysis of dextromethorphan metabolism in human saliva and urine to determine CYP2D6 phenotype and individual variability in N-demethylation and glucuronidation J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Dec 25;813(1-2):217-25. doi: 10.1016/j.jchromb.2004.09.040.
13 Classics in Chemical Neuroscience: Dextromethorphan (DXM). ACS Chem Neurosci. 2023 Jun 21;14(12):2256-2270. doi: 10.1021/acschemneuro.3c00088.
14 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
15 Physiologically based pharmacokinetic (PBPK) modeling of the role of CYP2D6 polymorphism for metabolic phenotyping with dextromethorphan. Front Pharmacol. 2022 Oct 24;13:1029073. doi: 10.3389/fphar.2022.1029073.
16 Physiologically-based pharmacokinetic modeling of dextromethorphan to investigate interindividual variability within CYP2D6 activity score groups. CPT Pharmacometrics Syst Pharmacol. 2022 Apr;11(4):494-511. doi: 10.1002/psp4.12776.

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