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

General Information of Drug (ID: DR5233)
Drug Name
Clomipramine
Synonyms
Chlomipramine; Chlorimipramine; Clomicalm; Clomipramina; Clomipraminum; Hydiphen; Monochlorimipramine; Anafranil base; G 34586; Anafranil (TN); Anafranil (free base); Clomipramina [INN-Spanish]; Clomipramine (INN); Clomipramine [INN:BAN]; Clomipraminum [INN-Latin]; 10,11-dihydro-3-chloro-5-(3-(dimethylamino)propyl)-5H-dibenz(b,f)azepine; 3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N,N-dimethylpropan-1-amine; 3-(3-Chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethyl-1-propanamine; 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine; 3-Chloro-5-(3-(dimethylamino)propyl)-10,11-dihydro-5H-dibenz(b,f)azepine; 3-Chloro-5-[3-(dimethylamino)propyl]-10,11-dihydro-5H-dibenz[b,f]azepine; 3-Chloroimipramine; 3-chloro-10,11-dihydro-N,N-dimethyl-5H-Dibenz(b,f)azepine-5-propanamine; 5H-Dibenz(b,f)azepine, 3-chloro-5-(3-(dimethylamino)propyl)-10,11-dihydro-(8CI)
Indication Depression [ICD11: 6A70-6A7Z] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 314.9 Topological Polar Surface Area 6.5
Heavy Atom Count 22 Rotatable Bond Count 4
Hydrogen Bond Donor Count 0 Hydrogen Bond Acceptor Count 2
Cross-matching ID
PubChem CID
2801
ChEBI ID
CHEBI:47780
CAS Number
303-49-1
TTD Drug ID
D0ZS8P
Formula
C19H23ClN2
Canonical SMILES
CN(C)CCCN1C2=CC=CC=C2CCC3=C1C=C(C=C3)Cl
InChI
InChI=1S/C19H23ClN2/c1-21(2)12-5-13-22-18-7-4-3-6-15(18)8-9-16-10-11-17(20)14-19(16)22/h3-4,6-7,10-11,14H,5,8-9,12-13H2,1-2H3
InChIKey
GDLIGKIOYRNHDA-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
10-OH-clomipramine DM006112
154699866
Oxidation - Aliphatic hydroxylation 1 [5]
2-hydroxyclomipramine DM006104
10246110
Oxidation - 2-hydroxylation 1 [5]
8-hydroxyclomipramine DM006106
11724232
Oxidation - 8-hydroxylation 1 [5]
8-OH-clomipramine DM006111
134222
Oxidation - Aromatic hydroxylation 1 [5]
Clomipramine N-oxide DM006110
29976360
Unclear - Unclear 1 [7]
Desmethylclomipramine DM006100
622606
Oxidation - N-demethylation 1 [5]
2-hydroxyclomipramine glucuronide DM006105
165361827
Conjugation - Glucuronidation 2 [5]
2-hydroxydesmethyl clomipramine DM006101
91617717
Oxidation - Demethylation 2 [5]
8-hydroxyclomipramine glucuronide DM006109 N. A. Conjugation - Glucuronidation 2 [5]
8-hydroxydesmethyl clomipramine DM006107
10018695
Unclear - Unclear 2 [5] , [2]
Didesmethylclomipramine DM006103
3085253
Oxidation - N-demethylation 2 [5]
2-hydroxydesmethyl clomipramine glucuronide DM006102
165361770
Conjugation - Glucuronidation 3 [5]
8-hyroxydesmethyl clomipramine glucuronide DM006108 N. A. Unclear - Unclear 3 [5]
⏷ Show the Full List of 13  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR009001 Clomipramine 2-hydroxyclomipramine Oxidation - 2-hydroxylation CYP2D6 [5]
MR009005 Clomipramine 8-hydroxyclomipramine Oxidation - 8-hydroxylation CYP2D6 [5]
MR009009 Clomipramine Desmethylclomipramine Oxidation - N-demethylation CYP3A4 ... [5]
MR009011 Clomipramine Clomipramine N-oxide Unclear - Unclear Unclear [7]
MR009012 Clomipramine 8-OH-clomipramine Oxidation - Aromatic hydroxylation CYP2D6 [5]
MR009013 Clomipramine 10-OH-clomipramine Oxidation - Aliphatic hydroxylation CYP2D6 [5]
MR009002 2-hydroxyclomipramine 2-hydroxydesmethyl clomipramine Oxidation - Demethylation CYP2D6 [5]
MR009004 2-hydroxyclomipramine 2-hydroxyclomipramine glucuronide Conjugation - Glucuronidation Unclear [5]
MR009006 8-hydroxyclomipramine 8-hydroxydesmethyl clomipramine Unclear - Unclear CYP3A4 ... [5], [2]
MR009008 8-hydroxyclomipramine 8-hydroxyclomipramine glucuronide Conjugation - Glucuronidation Unclear [5]
MR009010 Desmethylclomipramine Didesmethylclomipramine Oxidation - N-demethylation CYP1A2 [5]
MR009003 2-hydroxydesmethyl clomipramine 2-hydroxydesmethyl clomipramine glucuronide Conjugation - Glucuronidation Unclear [5]
MR009007 8-hydroxydesmethyl clomipramine 8-hyroxydesmethyl clomipramine glucuronide Unclear - Unclear Unclear [5]
⏷ Show the Full List of 13 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 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[3] , [4]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[5]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[4] , [6] , [3]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[4]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[2]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[6] , [2]
⏷ Show the Full List of 8  DME(s)
References
1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2398).
2 The effect of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients. J Clin Psychopharmacol. 2001 Dec;21(6):549-55.
3 Erythromycin interaction with risperidone or clomipramine in an adolescent. J Child Adolesc Psychopharmacol. 1996 Summer;6(2):133-8.
4 The biotransformation of clomipramine in vitro, identification of the cytochrome P450s responsible for the separate metabolic pathways. J Pharmacol Exp Ther. 1996 Jun;277(3):1659-64.
5 Pharmacogenomics knowledge for personalized medicine Clin Pharmacol Ther. 2012 Oct;92(4):414-7. doi: 10.1038/clpt.2012.96.
6 Serum clomipramine and desmethylclomipramine levels in a CYP2C19 and CYP2D6 intermediate metabolizer. Pharmacogenomics. 2017 May;18(7):601-605.
7 DrugBank(Pharmacology-Metabolism):Clomipramine

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