General Information of Drug (ID: DR1681)
Drug Name
Verapamil hydrochloride
Synonyms
Vasopten; Verabeta; Veracor; Verahexal; Veraloc; Veramil; Verapamil Ebewe; Verapamil HCl; Verapamil hydrochloride; Verapin; Verasal; Verasifar; Veratensin; Verdilac; Veroptinstada; Vetrimil; Vortac; Veramex; Verapamil [USAN:INN:BAN]; Verapamilo; Verapamilo [INN-Spanish]; Verapamilum; Verapamilum [INN-Latin]; Verelan; Verelan PM; Verpamil; 5-((3,4-Dimethoxyphenethyl)methylamino)-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile; 52-53-9; Berkatens; CCRIS 6749; CP-16533-1; Calan; Calcan; Cardiagutt; Covera-HS; D-365; Dignover; Dilacoran; Falicard; Finoptin; Geangin; Iproveratril; Isoptimo; Isoptin; Isoptine; Isotopin; Izoptin; Lekoptin; Novo-Veramil; Quasar; Securon; Tarka; Univer; VERAPAMIL; Vasolan; (+/-)-VERAPAMIL HYDROCHLORIDE; 152-11-4; Anpec; Calaptin; Calcan hydrochloride; Cardiabeltin; Cardioprotect; Caveril; Civicor; Coraver; Corpamil; Durasoptin; Elthon; Flamon; Harteze; Hexasoptin; Hormitol; Ikacor; Ikapress; Inselon; Isoptino; Jenapamil; Lodixal; Magotiron; Manidon; Ormil; Praecicor; Rapam; Robatelan; Univex; Vasomil
Indication Essential hypertension [ICD11: BA00] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 491.1 Topological Polar Surface Area 64
Heavy Atom Count 34 Rotatable Bond Count 13
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 6
Cross-matching ID
PubChem CID
62969
CAS Number
152-11-4
TTD Drug ID
D0R0FE
Formula
C27H39ClN2O4
Canonical SMILES
CC(C)C(CCCN(C)CCC1=CC(=C(C=C1)OC)OC)(C#N)C2=CC(=C(C=C2)OC)OC.Cl
InChI
1S/C27H38N2O4.ClH/c1-20(2)27(19-28,22-10-12-24(31-5)26(18-22)33-7)14-8-15-29(3)16-13-21-9-11-23(30-4)25(17-21)32-6;/h9-12,17-18,20H,8,13-16H2,1-7H3;1H
InChIKey
DOQPXTMNIUCOSY-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
Norverapamil DM005256
104972
Oxidation - N-demethylation 1 [6]
O-Desmethylverapamil (D-702) DM005258
131750721
Oxidation - O-demethylation 1 [6]
O-Desmethylverapamil (D-703) DM005259
625729
Oxidation - O-demethylation 1 [6]
Verapamil metabolite D-617 DM005252
93168
Oxidation - N-dealkylation 1 [6]
Verapamil metabolite D-620 DM005254
161569
Oxidation - N-dealkylation 2 [6]
Verapamil metabolite D-715 DM005257
10410215
Oxidation - O-demethylation 2 [6]
Verapamil metabolite PR-25 DM005253
10016311
Oxidation - O-demethylation 2 [6]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR005644 Verapamil hydrochloride Verapamil metabolite D-617 Oxidation - N-dealkylation CYP2C18 [6]
MR005647 Verapamil hydrochloride Norverapamil Oxidation - N-demethylation CYP1A2 ... [6]
MR005650 Verapamil hydrochloride O-Desmethylverapamil (D-702) Oxidation - O-demethylation CYP2C8 ... [6]
MR005652 Verapamil hydrochloride O-Desmethylverapamil (D-703) Oxidation - O-demethylation CYP2C8 ... [6]
MR005648 Norverapamil Verapamil metabolite D-620 Oxidation - N-dealkylation CYP2C8 [6]
MR005649 Norverapamil Verapamil metabolite D-715 Oxidation - O-demethylation CYP2C8 [6]
MR005651 O-Desmethylverapamil (D-702) Verapamil metabolite D-620 Oxidation - N-dealkylation CYP3A4. CYP3A5 ... [6]
MR005645 Verapamil metabolite D-617 Verapamil metabolite PR-25 Oxidation - O-demethylation Unclear [6]
MR005646 Verapamil metabolite D-617 Verapamil metabolite D-620 Oxidation - N-dealkylation CYP3A5 ... [6]
⏷ Show the Full List of 9 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 2C18 (CYP2C18) DME0017 Homo sapiens
CP2CI_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 2E1 (CYP2E1) DME0013 Homo sapiens
CP2E1_HUMAN
1.14.14.1
[3]
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
[7]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[8]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[9]
Unclear metabolic mechanism (DME-unclear) DME1384 Bacteroides vulgatus Not Available Not Available [10]
⏷ Show the Full List of 11  DME(s)
References
1 Verapamil Hydrochloride was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
3 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
4 Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
5 Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
6 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.
7 Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
8 Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Drug Metab Dispos. 2004 Feb;32(2):259-66.
9 Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
10 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.

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