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

General Information of Drug (ID: DR0514)
Drug Name
Diphenhydramine
Synonyms
Dabylen; Debendrin; Dermistina; Dermodrin; Desentol; Diabenyl; Diabylen; Dibondrin; Difedryl; Difenhydramin; Dihidral; Diphantine; Drylistan; Dylamon; Etanautine; Histaxin; Hyadrine; Ibiodral; Medidryl; Mephadryl; Nausen; Novamina; Probedryl; Alledryl; Allergical; Amidryl; Antistominum; Antomin; Bagodryl; Baramine; Benachlor; Benadrin; Benadryl; Benapon; Benodin; Benodine; Benylan; Benylin; Benzantine; Benzhydramine; Benzhydraminum; Benzhydril; Benzhydroamina; Betramin; Syntedril; diphenhydramine; 2-(Benzhydryloxy)-N,N-dimethylethanamine; 58-73-1
Indication Meniere disease [ICD11: AB31] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 255.35 Topological Polar Surface Area 12.5
Heavy Atom Count 19 Rotatable Bond Count 6
Hydrogen Bond Donor Count 0 Hydrogen Bond Acceptor Count 2
Cross-matching ID
PubChem CID
3100
PubChem SID
9174 ; 511392 ; 608048 ; 3154507 ; 5021578 ; 7847366 ; 7849634 ; 7885212 ; 7979103 ; 8151972 ; 10508422 ; 10528411 ; 10544720 ; 11111059 ; 11111060 ; 11335543 ; 11360782 ; 11363874 ; 11366436 ; 11368998 ; 11371539 ; 11374238 ; 11377160 ; 11407308 ; 11427137 ; 11461754 ; 11466093 ; 11467213 ; 11484697 ; 11485906 ; 11488777 ; 11490216 ; 11492335 ; 11494794 ; 14749996 ; 25768169 ; 26713829 ; 26751623 ; 29222243 ; 46505484 ; 47440177 ; 47588927 ; 47810670 ; 47810671 ; 48035032 ; 48110379 ; 48110380 ; 48184925 ; 48184926 ; 48415909
ChEBI ID
CHEBI:4636
CAS Number
58-73-1
TTD Drug ID
D01FGR
Formula
C17H21NO
Canonical SMILES
CN(C)CCOC(C1=CC=CC=C1)C2=CC=CC=C2
InChI
1S/C17H21NO/c1-18(2)13-14-19-17(15-9-5-3-6-10-15)16-11-7-4-8-12-16/h3-12,17H,13-14H2,1-2H3
InChIKey
ZZVUWRFHKOJYTH-UHFFFAOYSA-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
Diphenhydramine N-glucuronide DM000109
178420
Conjugation - Glucuronidation 1 [5] , [6]
N-acetyldidesmethyldiphenhydramine DM000110 N. A. Unclear 1 [7]
N-desmethyldiphenhydramine DM000105
40791
Oxidation - N-Demethylation 1 [4] , [5] , [8] , [6]
N,N-didesmethyldiphenhydramine DM000106
36060
Oxidation - N-Demethylation 2 [4] , [5] , [8]
Diphenylmethoxyacetic acid DM000107
597513
Oxidation - Oxidation 3 [5] , [8]
N-acetyl-N-desmethyldiphenhydramine DM000108 N. A. Conjugation - Acetylation 3 [5] , [8]
Unclear DM009999 N. A. Conjugation - Conjugation 4 [9]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR000876 Diphenhydramine N-desmethyldiphenhydramine Oxidation - N-Demethylation CYP2D6 ... [4], [5], [8], [6]
MR000877 Diphenhydramine Diphenhydramine N-glucuronide Conjugation - Glucuronidation UGT [5], [6]
MR000878 Diphenhydramine N-acetyldidesmethyldiphenhydramine Unclear Unclear [7]
MR000872 N-desmethyldiphenhydramine N,N-didesmethyldiphenhydramine Oxidation - N-Demethylation CYP2D6 ... [4], [5], [8]
MR000873 N,N-didesmethyldiphenhydramine Diphenylmethoxyacetic acid Oxidation - Oxidation Unclear [5], [8]
MR000874 N,N-didesmethyldiphenhydramine N-acetyl-N-desmethyldiphenhydramine Conjugation - Acetylation Unclear [5], [8]
MR000875 Diphenylmethoxyacetic acid . Conjugation - Conjugation Unclear [9]
⏷ Show the Full List of 7 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[2]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[3]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[4]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[5]
Prostaglandin G/H synthase 1 (COX-1) DME0091 Homo sapiens
PGH1_HUMAN
1.14.99.1
[5]
References
1 Diphenhydramine was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation Drug Metab Dispos. 2007 Jan;35(1):72-8. doi: 10.1124/dmd.106.012088.
3 Pharmacogenomics in psychiatry: implications for practice. Recent Pat Biotechnol. 2014;8(2):152-9.
4 Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metab Dispos. 2007 Jan;35(1):72-8.
5 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.
6 Non-invasive skin sampling detects systemically administered drugs in humans. PLoS One. 2022 Jul 26;17(7):e0271794. doi: 10.1371/journal.pone.0271794.
7 Metabolism of the ethanolamine-type antihistamine diphenhydramine (Benadryl) by the fungus Cunninghamella elegans Appl Microbiol Biotechnol. 2000 Mar;53(3):310-5. doi: 10.1007/s002530050026.
8 Bioconcentration, metabolism and effects of diphenhydramine on behavioral and biochemical markers in crucian carp (Carassius auratus) Sci Total Environ. 2016 Feb 15;544:400-9. doi: 10.1016/j.scitotenv.2015.11.132.
9 American Society of Health System Pharmacists; AHFS Drug Information 2010. Bethesda, MD. (2010), p. 2511

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