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

General Information of Drug (ID: DR0095)
Drug Name
Amitriptyline hydrochloride
Synonyms
Amavil; Ami-Anelun; Amilit; Amineurin; Amiplin; Amiprin; Amitid; Amitrip; Amitriptyline HCl; Amitriptyline hydrochloride; Amyline; Amyzol; Anapsique; Annoyltin; Apo-Amitriptyline; Belpax; Daprimen; Domical; Elatrol; Elatrolet; Elavil hydrochloride; Enafon; Etrafon; Etravil; Kyliran; Larozyl; Lentizol; Levate; Maxivalet; Miketorin; Mitaptyline; Novoprotect; Pinsanu; Pinsaun; Rantoron; Saroten; Sarotena; Syneudon; Teperin; Trepiline; Triavil; Tridep; Tripta; Triptizol; Trynol; Tryptine; Tryptizol; Trytomer; Vanatrip; Yamanouchi; Adepress; Adepril; Amitril; Amitriptyline; Amitriprolidine; Amitriptilina; Amitriptilina [INN-Spanish]; Amitriptilina [Italian]; Amitriptylin; Amitriptylin [German]; Amitriptyline [INN:BAN]; Amitriptylinum; Amitriptylinum [INN-Latin]; Amitryptiline; Amitryptyline; Amytriptiline; Amytriptylin; Damilan; Damilen; Damitriptyline; Elanil; Elavil; Flavyl; Lantron; Laroxil; MK 230; Proheptadiene; Redomex; Ro 4-1575; Sarotex; Seroten; Triptanol; Triptilin; Triptisol; Tryptanol; 50-48-6; 549-18-8
Indication Depression [ICD11: 6A71] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 313.9 Topological Polar Surface Area 3.2
Heavy Atom Count 22 Rotatable Bond Count 3
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 1
Cross-matching ID
PubChem CID
11065
ChEBI ID
CHEBI:2667
CAS Number
549-18-8
TTD Drug ID
D0Y5UG
Formula
C20H24ClN
Canonical SMILES
CN(C)CCC=C1C2=CC=CC=C2CCC3=CC=CC=C31.Cl
InChI
1S/C20H23N.ClH/c1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20;/h3-6,8-12H,7,13-15H2,1-2H3;1H
InChIKey
KFYRPLNVJVHZGT-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
(E)-10-hydroxyamitriptyline DM018043 N. A. Unclear - Unclear 1 [11] , [12]
(Z)-10-hydroxyamitriptyline DM018042 N. A. Unclear - Unclear 1 [11] , [12]
Nortriptyline DM018038 N. A. Unclear - Unclear 1 [11] , [12]
(E)-10-hydroxynortriptyline DM018040 N. A. Unclear - Unclear 2 [11] , [12]
(Z)-10-hydroxynortriptyline DM018041 N. A. Unclear - Unclear 2 [11] , [12]
Demethylnortriptyline DM018039 N. A. Unclear - Unclear 2 [11] , [12]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR009854 Amitriptyline hydrochloride Nortriptyline Unclear - Unclear CYP2C19 [11], [12]
MR009858 Amitriptyline hydrochloride (Z)-10-hydroxyamitriptyline Unclear - Unclear Unclear [11], [12]
MR009860 Amitriptyline hydrochloride (E)-10-hydroxyamitriptyline Unclear - Unclear CYP2D6 [11], [12]
MR009861 (E)-10-hydroxyamitriptyline (E)-10-hydroxynortriptyline Unclear - Unclear CYP2D6 [11], [12]
MR009859 (Z)-10-hydroxyamitriptyline (Z)-10-hydroxynortriptyline Unclear - Unclear Unclear [11], [12]
MR009855 Nortriptyline Demethylnortriptyline Unclear - Unclear Unclear [11], [12]
MR009856 Nortriptyline (E)-10-hydroxynortriptyline Unclear - Unclear Unclear [11], [12]
MR009857 Nortriptyline (Z)-10-hydroxynortriptyline Unclear - Unclear Unclear [11], [12]
⏷ 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
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[2]
Cytochrome P450 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_HUMAN
1.14.14.1
[3]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[4]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[5]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[6]
Cytochrome P450 2E1 (CYP2E1) DME0013 Homo sapiens
CP2E1_HUMAN
1.14.14.1
[7]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[6]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[8]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[9]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[10]
⏷ Show the Full List of 10  DME(s)
References
1 Nortriptyline Hydrochloride was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 The genetic profiles of CYP1A1, CYP1A2 and CYP2E1 enzymes as susceptibility factor in xenobiotic toxicity in Turkish population. Saudi Pharm J. 2017 Feb;25(2):294-297.
3 Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37.
4 The xenobiotic inhibitor profile of cytochrome P4502C8. Br J Clin Pharmacol. 2000 Dec;50(6):573-80.
5 Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997 Feb;43(2):137-44.
6 Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67.
7 Five distinct human cytochromes mediate amitriptyline N-demethylation in vitro: dominance of CYP 2C19 and 3A4. J Clin Pharmacol. 1998 Feb;38(2):112-21.
8 Effects of cytochrome b(5) on drug oxidation activities of human cytochrome P450 (CYP) 3As: similarity of CYP3A5 with CYP3A4 but not CYP3A7. Biochem Pharmacol. 2003 Dec 15;66(12):2333-40.
9 A study on CYP2C19 and CYP2D6 polymorphic effects on pharmacokinetics and pharmacodynamics of amitriptyline in healthy Koreans. Clin Transl Sci. 2017 Mar;10(2):93-101.
10 Liquid chromatography-tandem mass spectrometry method for measurement of nicotine N-glucuronide: a marker for human UGT2B10 inhibition. J Pharm Biomed Anal. 2011 Jul 15;55(5):964-71.
11 CYP2D6 and CYP2C19 genotypes and amitriptyline metabolite ratios in a series of medicolegal autopsies
12 Amitriptyline Therapy and CYP2D6 and CYP2C19 Genotype

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