Record Information
Version3.6
Creation Date2006-02-16 09:20:18 UTC
Update Date2013-05-29 19:32:26 UTC
HMDB IDHMDB01850
Secondary Accession Numbers
  • HMDB14799
Metabolite Identification
Common NameVerapamil
DescriptionVerapamil 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 ).
Structure
Thumb
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 FormulaC27H38N2O4
Average Molecular Weight454.6016
Monoisotopic Molecular Weight454.283157714
IUPAC Name2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile
Traditional IUPAC Nameveraβ
CAS Registry Number52-53-9
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 KeySGTNSNPWRIOYBX-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Homomonocyclic Compounds
ClassPhenols and Derivatives
Sub ClassBenzenediols
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 ParentCatecholamines and Derivatives
Ontology
StatusExpected 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
StateSolid
Experimental Properties
PropertyValueReference
Melting Point< 25 °CPhysProp
Boiling Point243-246 °C at 1.00E-02 mm HgPhysProp
Water Solubility4.47 mg/LNot Available
LogP3.79HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility0.0039 g/LALOGPS
logP5.23ALOGPS
logP5.04ChemAxon
logS-5.1ALOGPS
pKa (strongest basic)9.68ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count6ChemAxon
hydrogen donor count0ChemAxon
polar surface area63.95ChemAxon
rotatable bond count13ChemAxon
refractivity132.65ChemAxon
polarizability51.7ChemAxon
Spectra
Spectra
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Adipose Tissue
  • Bladder
  • Brain
  • Fibroblasts
  • Intestine
  • Kidney
  • Liver
  • Neuron
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Stratum Corneum
  • Testes
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReference
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00661
  • Not Applicable
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00661
  • Not Applicable
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00661
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022708
KNApSAcK IDNot Available
Chemspider ID2425
KEGG Compound IDC07188
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkVerapamil
NuGOwiki LinkHMDB01850
Metagene LinkHMDB01850
METLIN ID3009
PubChem Compound2520
PDB IDNot Available
ChEBI ID9948
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. 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
  2. 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
  3. 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
  4. Miller MR, Withers R, Bhamra R, Holt DW: Verapamil and breast-feeding. Eur J Clin Pharmacol. 1986;30(1):125-6. Pubmed: 3709626
  5. 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
  6. 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
  7. 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
  8. Glusa E: Effect of verapamil on platelet aggregation. Folia Haematol Int Mag Klin Morphol Blutforsch. 1988;115(4):469-73. Pubmed: 2465955
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  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
  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
  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
  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
  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
  22. Bellamy WT: P-glycoproteins and multidrug resistance. Annu Rev Pharmacol Toxicol. 1996;36:161-83. Pubmed: 8725386

Enzymes

Gene Name:
CYP3A5
Uniprot ID:
P20815
Gene Name:
CYP1A2
Uniprot ID:
P05177
Gene Name:
CA1
Uniprot ID:
P00915

Transporters

Gene Name:
SLC22A5
Uniprot ID:
O76082