Human Metabolome Database Version 3.5

Showing metabocard for Verapamil (HMDB01850)

Record Information
Version 3.5
Creation Date 2006-02-16 02:20:18 -0700
Update Date 2013-05-29 13:32:26 -0600
HMDB ID HMDB01850
Secondary Accession Numbers
  • HMDB14799
Metabolite Identification
Common Name Verapamil
Description Verapamil is only found in individuals that have used or taken this drug. Verapamil is a calcium channel blocker that is a class IV anti-arrhythmia agent. [PubChem]Verapamil inhibits voltage-dependent calcium channels. Specifically, its effect on L-type calcium channels in the heart causes a reduction in ionotropy and chronotropy, thuis reducing heart rate and blood pressure. Verapamil's mechanism of effect in cluster headache is thought to be linked to its calcium-channel blocker effect, but which channel subtypes are involved is presently not known. [PubChem] Calcium channel antagonists can be quite toxic. In the management of poisoning, early recognition is critical. Calcium channel antagonists are frequently prescribed, and the potential for serious morbidity and mortality with over dosage is significant. Ingestion of these agents should be suspected in any patient who presents in an overdose situation with unexplained hypotension and conduction abnormalities. The potential for toxicity should be noted in patients with underlying hepatic or renal dysfunction who are receiving therapeutic doses. (PMID 8213877 Link_out).
Structure Thumb
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  1. Akilen
  2. Anpec
  3. Apo-Verap
  4. Arpamyl LP
  5. Berkatens
  6. Calan
  7. Calan SR
  8. Calaptin
  9. Calaptin 240 SR
  10. Calcan
  11. Cardiabeltin
  12. Cardiagutt
  13. Cardibeltin
  14. Cardioprotect
  15. Caveril
  16. Civicor
  17. Civicor Retard
  18. Coraver
  19. Cordilox
  20. Cordilox SR
  21. Corpamil
  22. Covera-Hs
  23. D-365
  24. delta-365
  25. Dignover
  26. Dilacoran
  27. Dilacoran HTA
  28. Durasoptin
  29. Elthon
  30. Falicard
  31. Finoptin
  32. Flamon
  33. Geangin
  34. Harteze
  35. Hexasoptin
  36. Hexasoptin Retard
  37. Hormitol
  38. Ikacor
  39. Ikapress
  40. Inselon
  41. Iproveratril
  42. Isoptin
  43. Isoptin Retard
  44. Isoptin SR
  45. Isoptine
  46. Isoptino
  47. Isotopin
  48. Izoptin
  49. Jenapamil
  50. Lekoptin
  51. Lodixal
  52. Magotiron
  53. Manidon
  54. Manidon Retard
  55. Novapamyl LP
  56. Novo-Veramil
  57. Nu-Verap
  58. Ormil
  59. Praecicor
  60. Quasar
  61. Rapam
  62. Robatelan
  63. Securon
  64. Tarka
  65. Univer
  66. Univex
  67. Vasolan
  68. Vasomil
  69. Vasopten
  70. Vera-Sanorania
  71. Verabeta
  72. Veracaps SR
  73. Veracor
  74. Verahexal
  75. Veraloc
  76. Veramex
  77. Veramil
  78. Verapamil
  79. Verapamil Acis
  80. Verapamil AL
  81. Verapamil Atid
  82. Verapamil Basics
  83. Verapamil Ebewe
  84. Verapamil HCl
  85. Verapamil Henning
  86. Verapamil Injection
  87. Verapamil MSD
  88. Verapamil NM
  89. Verapamil NM Pharma
  90. Verapamil Nordic
  91. Verapamil PB
  92. Verapamil Riker
  93. Verapamil SR
  94. Verapamil Verla
  95. Verapamil-AbZ
  96. Verapamilo
  97. Verapamilum
  98. Verapin
  99. Verapress 240 SR
  100. Verasal
  101. Verasifar
  102. Veratensin
  103. Verdilac
  104. Verelan
  105. Verelan PM
  106. Verelan SR
  107. Veroptinstada
  108. Verpamil
  109. Vetrimil
  110. Vortac
Chemical Formula C27H38N2O4
Average Molecular Weight 454.6016
Monoisotopic Molecular Weight 454.283157714
IUPAC Name 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile
Traditional IUPAC Name veraβ
CAS Registry Number 52-53-9
SMILES COC1=C(OC)C=C(CCN(C)CCCC(C#N)(C(C)C)C2=CC(OC)=C(OC)C=C2)C=C1
InChI Identifier InChI=1S/C27H38N2O4/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
InChI Key SGTNSNPWRIOYBX-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Aromatic Homomonocyclic Compounds
Class Phenols and Derivatives
Sub Class Benzenediols
Other Descriptors
  • Aromatic Homopolycyclic Compounds
  • Organic Compounds
  • Phenylbutylamines
  • cyanides(ChEBI)
  • tertiary amine(ChEBI)
Substituents
  • Alkyl Aryl Ether
  • Anisole
  • Benzyl Cyanide
  • Nitrile
  • Phenethylamine
  • Tertiary Aliphatic Amine (Trialkylamine)
Direct Parent Catecholamines and Derivatives
Ontology
Status Expected and Not Quantified
Origin
  • Drug
Biofunction
  • Anti-Arrhythmia Agents
  • Antiarrhythmic Agents
  • Calcium Channel Blockers
  • Vasodilator Agents
Application
  • Pharmaceutical
Cellular locations
  • Membrane (predicted from logP)
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point < 25 °C PhysProp
Boiling Point 243-246 °C at 1.00E-02 mm Hg PhysProp
Water Solubility 4.47 mg/L Not Available
LogP 3.79 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
LogP 5.23 ALOGPS
LogP 5.04 ChemAxon
LogS -5.06 ALOGPS
pKa (strongest basic) 9.68 ChemAxon
Hydrogen Acceptor Count 6 ChemAxon
Hydrogen Donor Count 0 ChemAxon
Polar Surface Area 63.95 A2 ChemAxon
Rotatable Bond Count 13 ChemAxon
Refractivity 132.65 ChemAxon
Polarizability 51.7 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge 1 ChemAxon
Spectra
1H NMR Spectrum
MS/MS Spectrum Quattro_QQQ 10
MS/MS Spectrum Quattro_QQQ 25
MS/MS Spectrum Quattro_QQQ 40
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 10
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 20
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 30
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 40
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 50
MS/MS Spectrum LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies)
MS/MS Spectrum LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies)
MS/MS Spectrum LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies)
MS/MS Spectrum LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies)
MS/MS Spectrum LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies)
[1H,13C] 2D NMR Spectrum
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Bladder
  • Fibroblasts
  • Intestine
  • Neuron
  • Pancreas
  • Placenta
  • Testes
  • Kidney
  • Liver
  • Brain
  • Prostate
  • Adipose Tissue
  • Platelet
  • Stratum Corneum
Pathways Not Available
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Expected but not Quantified
Not Applicable Not Available Not Available Taking drug identified by DrugBank entry DB00661
  • Not Applicable
Urine Expected but not Quantified
Not Applicable Not Available Not Available Taking drug identified by DrugBank entry DB00661
  • Not Applicable
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease References None
Associated OMIM IDs None
DrugBank ID DB00661 Link_out
DrugBank Metabolite ID Not Available
Phenol Explorer Compound ID Not Available
Phenol Explorer Metabolite ID Not Available
FoodDB ID FDB022708
KNApSAcK ID Not Available
Chemspider ID 2425 Link_out
KEGG Compound ID C07188 Link_out
BioCyc ID Not Available
BiGG ID Not Available
Wikipedia Link Verapamil Link_out
NuGOwiki Link HMDB01850 Link_out
Metagene Link HMDB01850 Link_out
METLIN ID 3009 Link_out
PubChem Compound 2520 Link_out
PDB ID Not Available
ChEBI ID 9948 Link_out
References
Synthesis Reference Not Available
Material Safety Data Sheet (MSDS) Download (PDF)
General References
  1. Wang YH, Jones DR, Hall SD: Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71. Epub 2005 Feb 2. Pubmed: 15689501 Link_out
  2. Byerly WG, Hartmann A, Foster DE, Tannenbaum AK: Verapamil in the treatment of maternal paroxysmal supraventricular tachycardia. Ann Emerg Med. 1991 May;20(5):552-4. Pubmed: 2024796 Link_out
  3. Miller MR, Withers R, Bhamra R, Holt DW: Verapamil and breast-feeding. Eur J Clin Pharmacol. 1986;30(1):125-6. Pubmed: 3709626 Link_out
  4. Takano A, Kusuhara H, Suhara T, Ieiri I, Morimoto T, Lee YJ, Maeda J, Ikoma Y, Ito H, Suzuki K, Sugiyama Y: Evaluation of in vivo P-glycoprotein function at the blood-brain barrier among MDR1 gene polymorphisms by using 11C-verapamil. J Nucl Med. 2006 Sep;47(9):1427-33. Pubmed: 16954549 Link_out
  5. Fakih H, MacLusky N, DeCherney A, Wallimann T, Huszar G: Enhancement of human sperm motility and velocity in vitro: effects of calcium and creatine phosphate. Fertil Steril. 1986 Nov;46(5):938-44. Pubmed: 3781011 Link_out
  6. Suzuki S, Nishimaki-Mogami T, Tamehiro N, Inoue K, Arakawa R, Abe-Dohmae S, Tanaka AR, Ueda K, Yokoyama S: Verapamil increases the apolipoprotein-mediated release of cellular cholesterol by induction of ABCA1 expression via Liver X receptor-independent mechanism. Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):519-25. Epub 2004 Jan 15. Pubmed: 14726413 Link_out
  7. Glusa E: Effect of verapamil on platelet aggregation. Folia Haematol Int Mag Klin Morphol Blutforsch. 1988;115(4):469-73. Pubmed: 2465955 Link_out
  8. Ceccato A, Chiap P, Hubert P, Toussaint B, Crommen J: Automated determination of verapamil and norverapamil in human plasma with on-line coupling of dialysis to high-performance liquid chromatography and fluorometric detection. J Chromatogr A. 1996 Oct 25;750(1-2):351-60. Pubmed: 8938391 Link_out
  9. Nanni G, Panocchia N, Tacchino R, Foco M, Piccioni E, Castagneto M: Increased incidence of infection in verapamil-treated kidney transplant recipients. Transplant Proc. 2000 May;32(3):551-3. Pubmed: 10812109 Link_out
  10. Affolter H, Burkard WP, Pletscher A: Verapamil, an antagonist at 5-hydroxytryptamine receptors of human blood platelets. Eur J Pharmacol. 1985 Jan 22;108(2):157-62. Pubmed: 3156755 Link_out
  11. Rumiantsev DO, Piotrovskii VK, Riabokon' OS, Metelitsa VI: [Comparison of the verapamil concentration of human blood serum and saliva] Farmakol Toksikol. 1987 Jan-Feb;50(1):85-9. Pubmed: 3556560 Link_out
  12. Gramatte T, Oertel R: Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil. Clin Pharmacol Ther. 1999 Sep;66(3):239-45. Pubmed: 10511059 Link_out
  13. Hsiao P, Sasongko L, Link JM, Mankoff DA, Muzi M, Collier AC, Unadkat JD: Verapamil P-glycoprotein transport across the rat blood-brain barrier: cyclosporine, a concentration inhibition analysis, and comparison with human data. J Pharmacol Exp Ther. 2006 May;317(2):704-10. Epub 2006 Jan 13. Pubmed: 16415090 Link_out
  14. von Richter O, Greiner B, Fromm MF, Fraser R, Omari T, Barclay ML, Dent J, Somogyi AA, Eichelbaum M: Determination of in vivo absorption, metabolism, and transport of drugs by the human intestinal wall and liver with a novel perfusion technique. Clin Pharmacol Ther. 2001 Sep;70(3):217-27. Pubmed: 11557909 Link_out
  15. Narang PK, Blumhardt CL, Doran AR, Pickar D: Steady-state cerebrospinal fluid transfer of verapamil and metabolites in patients with schizophrenia. Clin Pharmacol Ther. 1988 Nov;44(5):550-7. Pubmed: 3180637 Link_out
  16. Takeda H, Yamazaki Y, Akahane M, Igawa Y, Ajisawa Y, Nishizawa O: Role of the beta(3)-adrenoceptor in urine storage in the rat: comparison between the selective beta(3)-adrenoceptor agonist, CL316, 243, and various smooth muscle relaxants. J Pharmacol Exp Ther. 2000 Jun;293(3):939-45. Pubmed: 10869395 Link_out
  17. Szymanski W, Skublicki S, Jankowski A, Kotzbach R: [Pharmacokinetic investigations of verapamil used as a concomitant drug in treatment of premature labor] Ginekol Pol. 1992 Apr;63(4):166-71. Pubmed: 1303922 Link_out
  18. Wang YH, Jones DR, Hall SD: Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Drug Metab Dispos. 2004 Feb;32(2):259-66. Pubmed: 14744949 Link_out
  19. Dumestre-Toulet V, Cirimele V, Gromb S, Belooussoff T, Lavault D, Ludes B, Kintz P: Last performance with VIAGRA: post-mortem identification of sildenafil and its metabolites in biological specimens including hair sample. Forensic Sci Int. 2002 Mar 28;126(1):71-6. Pubmed: 11955836 Link_out
  20. Bauer LA, Horn JR, Maxon MS, Easterling TR, Shen DD, Strandness DE Jr: Effect of metoprolol and verapamil administered separately and concurrently after single doses on liver blood flow and drug disposition. J Clin Pharmacol. 2000 May;40(5):533-43. Pubmed: 10806607 Link_out
  21. Hofer CA, Smith JK, Tenholder MF: Verapamil intoxication: a literature review of overdoses and discussion of therapeutic options. Am J Med. 1993 Oct;95(4):431-8. Pubmed: 8213877 Link_out
  22. Bellamy WT: P-glycoproteins and multidrug resistance. Annu Rev Pharmacol Toxicol. 1996;36:161-83. Pubmed: 8725386 Link_out

Enzymes
Name: Cytochrome P450 3A5
Reactions: Not Available
Gene Name: CYP3A5
Uniprot ID: P20815 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Cytochrome P450 1A2
Reactions: Not Available
Gene Name: CYP1A2
Uniprot ID: P05177 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Voltage-dependent L-type calcium channel subunit alpha-1D
Reactions: Not Available
Gene Name: CACNA1D
Uniprot ID: Q01668 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Carbonic anhydrase 1
Reactions: Not Available
Gene Name: CA1
Uniprot ID: P00915 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Potassium voltage-gated channel subfamily H member 2
Reactions: Not Available
Gene Name: KCNH2
Uniprot ID: Q12809 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Voltage-dependent L-type calcium channel subunit alpha-1C
Reactions: Not Available
Gene Name: CACNA1C
Uniprot ID: Q13936 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: ATP-sensitive inward rectifier potassium channel 11
Reactions: Not Available
Gene Name: KCNJ11
Uniprot ID: Q14654 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Voltage-dependent L-type calcium channel subunit alpha-1F
Reactions: Not Available
Gene Name: CACNA1F
Uniprot ID: O60840 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Voltage-dependent T-type calcium channel subunit alpha-1G
Reactions: Not Available
Gene Name: CACNA1G
Uniprot ID: O43497 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Voltage-dependent T-type calcium channel subunit alpha-1I
Reactions: Not Available
Gene Name: CACNA1I
Uniprot ID: Q9P0X4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Voltage-dependent L-type calcium channel subunit alpha-1S
Reactions: Not Available
Gene Name: CACNA1S
Uniprot ID: Q13698 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Voltage-dependent L-type calcium channel subunit beta-1
Reactions: Not Available
Gene Name: CACNB1
Uniprot ID: Q02641 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Voltage-dependent L-type calcium channel subunit beta-2
Reactions: Not Available
Gene Name: CACNB2
Uniprot ID: Q08289 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Voltage-dependent L-type calcium channel subunit beta-3
Reactions: Not Available
Gene Name: CACNB3
Uniprot ID: P54284 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Voltage-dependent L-type calcium channel subunit beta-4
Reactions: Not Available
Gene Name: CACNB4
Uniprot ID: O00305 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Voltage-dependent calcium channel gamma-1 subunit
Reactions: Not Available
Gene Name: CACNG1
Uniprot ID: Q06432 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Sodium channel protein type 5 subunit alpha
Reactions: Not Available
Gene Name: SCN5A
Uniprot ID: Q14524 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Transporters
Name: Solute carrier family 22 member 5
Reactions: Not Available
Gene Name: SLC22A5
Uniprot ID: O76082 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA