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

General Information of Drug (ID: DR1181)
Drug Name
Nortriptyline hydrochloride
Synonyms
Noramitriptyline; Noritren; Nortriptilina [DCIT]; Nortriptyline [INN:BAN]; Nortriptylinum; Nortriptylinum [INN-Latin]; Nortryptiline; Nortryptyline; Pamelor hydrochloride; Sensaval; Sesaval; nortriptyline; 72-69-5; BRN 2216786; CCRIS 9175; EINECS 200-788-8; UNII-BL03SY4LXB; AVENTYL HCL; Amitryptyline, demethyl-; Ateben; Avantyl; Aventyl; BL03SY4LXB; Demethylamitriptylene; Demethylamitriptyline; Demethylamitryptyline; Desitriptilina; Desmethylamitriptyline; Lumbeck; Ateben hydrochloride; Aventyl allegron; Aventyl hydrochloride; Lilly 38489; N 7048; Noramitriptyline hydrochloride; Nortab hydrochloride; Nortriptylin hydrochloride; Nortriptyline (hydrochloride); Nortriptyline Hcl; Nortriptyline hydrochloride; Nortriptyline monohydrochloride; Norzepine; Sensival; 00FN6IH15D; 894-71-3; Desmethylamitriptyline hydrochloride; MFCD00058024; MLS000069673; UNII-00FN6IH15D
Indication Depression [ICD11: 6A71] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 299.8 Topological Polar Surface Area 12
Heavy Atom Count 21 Rotatable Bond Count 3
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 1
Cross-matching ID
PubChem CID
441358
ChEBI ID
CHEBI:7641
CAS Number
894-71-3
TTD Drug ID
D04WFD
Formula
C19H22ClN
Canonical SMILES
CNCCC=C1C2=CC=CC=C2CCC3=CC=CC=C31.Cl
InChI
1S/C19H21N.ClH/c1-20-14-6-11-19-17-9-4-2-7-15(17)12-13-16-8-3-5-10-18(16)19;/h2-5,7-11,20H,6,12-14H2,1H3;1H
InChIKey
SHAYBENGXDALFF-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
Desmethylnortriptyline DM002271
160755
Unclear 1 [8] , [9]
E-10-hydroxydesmethylnortriptyline DM002272
6506716
Oxidation - N-Demethylation 2 [3] , [10]
Oxonortriptyline DM002273 N. A. Conjugation - Glycine Conjugation 3 [11] , [9]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001796 Nortriptyline hydrochloride Desmethylnortriptyline Unclear CYP1A2 ... [8], [9]
MR001794 Desmethylnortriptyline E-10-hydroxydesmethylnortriptyline Oxidation - N-Demethylation CYP3A4 ... [3], [10]
MR001795 E-10-hydroxydesmethylnortriptyline Oxonortriptyline Conjugation - Glycine Conjugation Unclear [11], [9]
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]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[5]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[6]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[7]
Prostaglandin G/H synthase 1 (COX-1) DME0091 Homo sapiens
PGH1_HUMAN
1.14.99.1
[3]
⏷ Show the Full List of 7  DME(s)
References
1 Nortriptyline Hydrochloride was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Hydroxylation and demethylation of the tricyclic antidepressant nortriptyline by cDNA-expressed human cytochrome P-450 isozymes. Drug Metab Dispos. 1997 Jun;25(6):740-4.
3 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.
4 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.
5 Cytochrome P-450 activities in human and rat brain microsomes. Brain Res. 2000 Feb 14;855(2):235-43.
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 In vivo age-related changes in hepatic drug-oxidizing capacity in humans. J Clin Pharm Ther. 1998 Aug;23(4):247-55.
8 Quantitative Modeling Analysis Demonstrates the Impact of CYP2C19 and CYP2D6 Genetic Polymorphisms on the Pharmacokinetics of Amitriptyline and Its Metabolite, Nortriptyline J Clin Pharmacol. 2019 Apr;59(4):532-540. doi: 10.1002/jcph.1344.
9 DrugBank(Pharmacology-Metabolism)Nortriptyline hydrochloride
10 Pharmacokinetics of nortriptyline and its 10-hydroxy metabolite in Chinese subjects of different CYP2D6 genotypes Clin Pharmacol Ther. 1998 Oct;64(4):384-90. doi: 10.1016/S0009-9236(98)90069-8.
11 A novel LC-MS/MS method for simultaneous estimation of obeticholic acid, glyco-obeticholic acid, tauro-obeticholic acid in human plasma and its application to a pharmacokinetic study J Sep Sci. 2021 Apr;44(7):1307-1323. doi: 10.1002/jssc.202001050.

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