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Record Information
Version2.0
Creation Date2009-07-30 17:59:14 UTC
Update Date2014-12-24 20:26:08 UTC
Accession NumberT3D3544
Identification
Common NameVerapamil
ClassSmall Molecule
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. (3).
Compound Type
  • Amine
  • Anti-Arrhythmia Agent
  • Calcium Channel Blocker
  • Cyanide Compound
  • Drug
  • Ether
  • Food Toxin
  • Metabolite
  • Nitrile
  • Organic Compound
  • Synthetic Compound
  • Vasodilator Agent
Chemical Structure
Thumb
Synonyms
Synonym
Akilen
Anpec
Apo-Verap
Arpamyl LP
Berkatens
Bosoptin
Calan
Calan SR
Calaptin
Calaptin 240 SR
Calcan
Cardiabeltin
Cardiagutt
Cardibeltin
Cardioprotect
Caveril
Civicor
Civicor Retard
Coraver
Cordilox
Cordilox SR
Corpamil
Covera-Hs
CP-16533-1
CP-165331
D-365
delta-365
Dignover
Dilacoran
Dilacoran HTA
Durasoptin
Elthon
Falicard
Finoptin
Flamon
Geangin
Harteze
Hexasoptin
Hexasoptin Retard
Hormitol
Ikacor
Ikapress
Inselon
Iproveratril
Isoptin
Isoptin Retard
Isoptin SR
Isoptine
Isoptino
Isotopin
Izoptin
Jenapamil
Lekoptin
Lodixal
Magotiron
Manidon
Manidon Retard
Novapamyl LP
Novo-Veramil
Nu-Verap
Ormil
Praecicor
Quasar
Rapam
Robatelan
Securon
Tarka
Univer
Univex
Vasolan
Vasomil
Vasopten
Vera-Sanorania
Verabeta
Veracaps SR
Veracor
Verahexal
Veraloc
Veramex
Veramil
Verapamil Acis
Verapamil AL
Verapamil Atid
Verapamil Basics
Verapamil Ebewe
Verapamil HCl
Verapamil Henning
Verapamil Injection
Verapamil MSD
Verapamil NM
Verapamil NM Pharma
Verapamil Nordic
Verapamil PB
Verapamil Riker
Verapamil SR
Verapamil Verla
Verapamil-AbZ
Verapamilo
Verapamilum
Verapin
Verapress 240 SR
Verasal
Verasifar
Veratensin
Verdilac
Verelan
Verelan PM
Verelan SR
Verisop
Vermin
Vermine
Verogalid
Verogalid ER
Veroptinstada
Verpamil
Vertab
Vetrimil
Vortac
Zolvera
Chemical FormulaC27H38N2O4
Average Molecular Mass454.602 g/mol
Monoisotopic Mass454.283 g/mol
CAS Registry Number52-53-9
IUPAC Name2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile
Traditional Nameveraβ
SMILESCOC1=C(OC)C=C(CCN(C)CCCC(C#N)(C(C)C)C2=CC(OC)=C(OC)C=C2)C=C1
InChI IdentifierInChI=1/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 KeyInChIKey=SGTNSNPWRIOYBX-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenylbutylamines. Phenylbutylamines are compounds containing a phenylbutylamine moiety, which consists of a phenyl group substituted at the fourth carbon by an butan-1-amine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylbutylamines
Direct ParentPhenylbutylamines
Alternative Parents
Substituents
  • Phenylbutylamine
  • Dimethoxybenzene
  • O-dimethoxybenzene
  • Phenethylamine
  • Phenylpropane
  • Anisole
  • Phenol ether
  • Phenoxy compound
  • Methoxybenzene
  • Alkyl aryl ether
  • Aralkylamine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Nitrile
  • Carbonitrile
  • Ether
  • Organic oxygen compound
  • Amine
  • Organic nitrogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Bladder
  • Brain
  • Fibroblasts
  • Intestine
  • Kidney
  • Liver
  • Neuron
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Stratum Corneum
  • Testes
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateLiquid
AppearanceNot Available
Experimental Properties
PropertyValue
Melting Point< 25°C
Boiling Point243-246°C at 1.00E-02 mm Hg
Solubility4.47 mg/L
LogP3.79
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 Area63.95 ŲChemAxon
Rotatable Bond Count13ChemAxon
Refractivity132.65 m³·mol⁻¹ChemAxon
Polarizability51.7 ųChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0cdu-4391500000-cd36ebd65bc8c7765961JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-004l-0702900000-6a46ea2d5eed6d8b01ebJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0006-4109800000-80d342090a0be3344e82JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-054w-0954400000-2def387c7c93ab211423JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-0a4i-0000900000-4cde9a4b3a4f83d16afcJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-0a4i-0000900000-980b47834e505d54a0e6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-066r-0902800000-ae024239c46b33917426JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-014i-0901000000-81d1159b3102cff76218JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-014i-0900000000-d9c344fee7b45b4030e6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positivesplash10-0gb9-0914000000-070bdb975910e9aae99cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positivesplash10-03di-0390000000-f41d80462c5d06c4f001JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positivesplash10-0097-2980000000-9a2ab0bcab33f7eaac6bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positivesplash10-0uxr-0900000000-252a9989a8511cb2db80JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positivesplash10-0f79-0900000000-4fd6ca2c6c19c3bbf8f0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0a4i-0000900000-4365a47b2dc2f86bb272JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0a4i-0000900000-e6a2b357160bf5b92c22JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-066r-0902400000-d8eac2ccd0a767c7e432JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-0901000000-688f3c2345c5d9ccb8a5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-0900000000-cd09f8a2be876936f662JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0uxr-0918000000-76641dd6dbc5cb05e79aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0000900000-05ea95eb1f39b6515212JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-066r-0902600000-a675e624692c25472ce8JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-014i-0901000000-70d820628d2613557239JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0gb9-0900000000-e3ca24cf75d574df08a8JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0uyi-0900000000-f3a9fa002c56d3e5689aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0zg0-2900000000-101e077b890671063633JSpectraViewer | MoNA
MSMass Spectrum (Electron Ionization)splash10-0udi-3519000000-b5e0b9e0caac5cb57222JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureOrally, 90‰ЫТ100% of Verapamil is absorbed. Intravenous.
Mechanism of ToxicityVerapamil 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.
MetabolismRoute of Elimination: Approximately 70% of an administered dose is excreted as metabolites in the urine and 16% or more in the feces within 5 days. About 3% to 4% is excreted in the urine as unchanged drug. Half Life: 2.8-7.4 hours
Toxicity ValuesLD50: 8 mg/kg (Intravenous, Mouse) (2)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesDrug used for the treatment of hypertension, angina, and cluster headache prophylaxis.
Minimum Risk LevelNot Available
Health EffectsCardiovascular: angina pectoris, AV block (2° & 3°), atrioventricular dissociation, CHF, pulmonary edema, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope. Digestive system: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia. Hemic and lymphatic: ecchymosis or bruising. Nervous system: cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, psychotic symptoms, shakiness, somnolence, extrapyramidal symptoms. Skin: arthralgia and rash, exanthema, hair loss, hyperkeratosis, macules, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme. Special senses: blurred vision, tinnitus. Urogenital: gynecomastia, galactorrhea/hyperprolactinemia, increased urination, spotty menstruation, impotence.
SymptomsThe resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
TreatmentTreatment of overdosage should be supportive. Beta-adrenergic stimulation or parenteral administration of calcium solutions may increase calcium ion flux across the slow channel and have been used effectively in treatment of deliberate overdosage with verapamil. In a few reported cases, overdose with calcium channel blockers has been associated with hypotension and bradycardia, initially refractory to atropine but becoming more responsive to this treatment when the patients received large doses (close to 1 gram/hour for more than 24 hours) of calcium chloride. Verapamil cannot be removed by hemodialysis. Clinically significant hypotensive reactions or high degree AV block should be treated with vasopressor agents or cardiac pacing, respectively. Asystole should be handled by the usual measures including cardiopulmonary resuscitation. (25)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00661
HMDB IDHMDB01850
PubChem Compound ID2520
ChEMBL IDCHEMBL197
ChemSpider ID2425
KEGG IDC07188
UniProt IDNot Available
OMIM ID
ChEBI ID9948
BioCyc IDNot Available
CTD IDNot Available
Stitch IDVerapamil
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkVerapamil
References
Synthesis Reference

Philippe Baudier, Arthur De Boeck, Jacques Fossion, “Novel galenic forms of verapamil, their preparation and medicines containing said novel galenic forms.” U.S. Patent US4859469, issued April, 1987.

MSDSLink
General References
  1. Bellamy WT: P-glycoproteins and multidrug resistance. Annu Rev Pharmacol Toxicol. 1996;36:161-83. [8725386 ]
  2. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  3. 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. [8213877 ]
  4. 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. [15689501 ]
  5. 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. [2024796 ]
  6. Miller MR, Withers R, Bhamra R, Holt DW: Verapamil and breast-feeding. Eur J Clin Pharmacol. 1986;30(1):125-6. [3709626 ]
  7. 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. [16954549 ]
  8. 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. [3781011 ]
  9. 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. [14726413 ]
  10. Glusa E: Effect of verapamil on platelet aggregation. Folia Haematol Int Mag Klin Morphol Blutforsch. 1988;115(4):469-73. [2465955 ]
  11. 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. [8938391 ]
  12. 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. [10812109 ]
  13. 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. [3156755 ]
  14. 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. [3556560 ]
  15. Gramatte T, Oertel R: Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil. Clin Pharmacol Ther. 1999 Sep;66(3):239-45. [10511059 ]
  16. 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. [16415090 ]
  17. 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. [11557909 ]
  18. 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. [3180637 ]
  19. 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. [10869395 ]
  20. 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. [1303922 ]
  21. 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. [14744949 ]
  22. 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. [11955836 ]
  23. 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. [10806607 ]
  24. Drugs.com [Link]
  25. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:
CA1
Uniprot ID:
P00915
Molecular Weight:
28870.0 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Ruschenschmidt C, Straub H, Kohling R, Siep E, Gorji A, Speckmann EJ: Reduction of human neocortical and guinea pig CA1-neuron A-type currents by organic calcium channel blockers. Neurosci Lett. 2004 Sep 16;368(1):57-62. [15342134 ]
  3. Mancilla EE, Galindo M, Fertilio B, Herrera M, Salas K, Gatica H, Goecke A: L-type calcium channels in growth plate chondrocytes participate in endochondral ossification. J Cell Biochem. 2007 May 15;101(2):389-98. [17243114 ]
  4. Palizvan MR, Fathollahi Y, Semnanian S: Epileptogenic insult causes a shift in the form of long-term potentiation expression. Neuroscience. 2005;134(2):415-23. [15961249 ]
  5. Zhang JM, Wu MN, Qi JS, Qiao JT: Amyloid beta-protein fragment 31-35 suppresses long-term potentiation in hippocampal CA1 region of rats in vivo. Synapse. 2006 Sep 15;60(4):307-13. [16786537 ]
General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
References
  1. Duan JJ, Ma JH, Zhang PH, Wang XP, Zou AR, Tu DN: Verapamil blocks HERG channel by the helix residue Y652 and F656 in the S6 transmembrane domain. Acta Pharmacol Sin. 2007 Jul;28(7):959-67. [17588331 ]
  2. Cheng HC, Incardona J, McCullough B: Isolated perfused and paced guinea pig heart to test for drug-induced changes of the QT interval. J Pharmacol Toxicol Methods. 2006 Nov-Dec;54(3):278-87. Epub 2006 Feb 28. [16507347 ]
  3. Schneider J, Hauser R, Andreas JO, Linz K, Jahnel U: Differential effects of human ether-a-go-go-related gene (HERG) blocking agents on QT duration variability in conscious dogs. Eur J Pharmacol. 2005 Apr 4;512(1):53-60. [15814090 ]
  4. Ridley JM, Dooley PC, Milnes JT, Witchel HJ, Hancox JC: Lidoflazine is a high affinity blocker of the HERG K(+)channel. J Mol Cell Cardiol. 2004 May;36(5):701-5. [15135665 ]
  5. Shimizu W, Aiba T, Antzelevitch C: Specific therapy based on the genotype and cellular mechanism in inherited cardiac arrhythmias. Long QT syndrome and Brugada syndrome. Curr Pharm Des. 2005;11(12):1561-72. [15892662 ]
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC502.21 uMNot AvailableBindingDB 50279753
IC504.78 uMNot AvailableBindingDB 50279753
References
  1. Lee BH, Lee CO, Kwon MJ, Yi KY, Yoo SE, Choi SU: Differential effects of the optical isomers of KR30031 on cardiotoxicity and on multidrug resistance reversal activity. Anticancer Drugs. 2003 Feb;14(2):175-81. [12569305 ]
  2. Verschraagen M, Koks CH, Schellens JH, Beijnen JH: P-glycoprotein system as a determinant of drug interactions: the case of digoxin-verapamil. Pharmacol Res. 1999 Oct;40(4):301-6. [10527640 ]
  3. Chang JH, Kochansky CJ, Shou M: The role of P-glycoprotein in the bioactivation of raloxifene. Drug Metab Dispos. 2006 Dec;34(12):2073-8. Epub 2006 Sep 7. [16959878 ]
  4. Zhang Y, Hu Y, Feng Y, Kodithuwakku ND, Fang W, Li Y, Huang W: The inhibitory and combinative mechanism of HZ08 with P-glycoprotein expressed on the membrane of Caco-2 cell line. Toxicol Appl Pharmacol. 2014 Jan 15;274(2):232-9. doi: 10.1016/j.taap.2013.11.019. Epub 2013 Dec 7. [24321342 ]
General Function:
Voltage-gated potassium channel activity
Specific Function:
This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium (By similarity). Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation.
Gene Name:
KCNJ11
Uniprot ID:
Q14654
Molecular Weight:
43540.375 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Yamada S, Kane GC, Behfar A, Liu XK, Dyer RB, Faustino RS, Miki T, Seino S, Terzic A: Protection conferred by myocardial ATP-sensitive K+ channels in pressure overload-induced congestive heart failure revealed in KCNJ11 Kir6.2-null mutant. J Physiol. 2006 Dec 15;577(Pt 3):1053-65. Epub 2006 Oct 12. [17038430 ]
  3. Shigeto M, Katsura M, Matsuda M, Ohkuma S, Kaku K: Nateglinide and mitiglinide, but not sulfonylureas, induce insulin secretion through a mechanism mediated by calcium release from endoplasmic reticulum. J Pharmacol Exp Ther. 2007 Jul;322(1):1-7. Epub 2007 Apr 4. [17409272 ]
General Function:
Serotonin:sodium symporter activity
Specific Function:
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
SLC6A4
Uniprot ID:
P31645
Molecular Weight:
70324.165 Da
References
  1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [9537821 ]
  2. Brown NL, Sirugue O, Worcel M: The effects of some slow channel blocking drugs on high affinity serotonin uptake by rat brain synaptosomes. Eur J Pharmacol. 1986 Apr 9;123(1):161-5. [2940099 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function.
Gene Name:
CACNA1C
Uniprot ID:
Q13936
Molecular Weight:
248974.1 Da
References
  1. Dilmac N, Hilliard N, Hockerman GH: Molecular determinants of frequency dependence and Ca2+ potentiation of verapamil block in the pore region of Cav1.2. Mol Pharmacol. 2004 Nov;66(5):1236-47. Epub 2004 Jul 30. [15286207 ]
  2. Patel MK, Clunn GF, Lymn JS, Austin O, Hughes AD: Effect of serum withdrawal on the contribution of L-type calcium channels (CaV1.2) to intracellular Ca2+ responses and chemotaxis in cultured human vascular smooth muscle cells. Br J Pharmacol. 2005 Jul;145(6):811-7. [15880143 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1F gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA).
Gene Name:
CACNA1F
Uniprot ID:
O60840
Molecular Weight:
220675.9 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle.
Gene Name:
CACNA1S
Uniprot ID:
Q13698
Molecular Weight:
212348.1 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Gene Name:
CACNB1
Uniprot ID:
Q02641
Molecular Weight:
65712.995 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Gene Name:
CACNB2
Uniprot ID:
Q08289
Molecular Weight:
73579.925 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Gene Name:
CACNB3
Uniprot ID:
P54284
Molecular Weight:
54531.425 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Gene Name:
CACNB4
Uniprot ID:
O00305
Molecular Weight:
58168.625 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Scaffold protein binding
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channel is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.
Gene Name:
CACNA1G
Uniprot ID:
O43497
Molecular Weight:
262468.62 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. Isoform alpha-1I gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. Gates in voltage ranges similar to, but higher than alpha 1G or alpha 1H (By similarity).
Gene Name:
CACNA1I
Uniprot ID:
Q9P0X4
Molecular Weight:
245100.8 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only as a multiple subunit complex.
Gene Name:
CACNG1
Uniprot ID:
Q06432
Molecular Weight:
25028.105 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular Weight:
56835.375 Da
References
  1. Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [9570190 ]
General Function:
Alpha1-adrenergic receptor activity
Specific Function:
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name:
ADRA1D
Uniprot ID:
P25100
Molecular Weight:
60462.205 Da
References
  1. Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [9570190 ]
General Function:
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular Weight:
226937.475 Da
References
  1. Milberg P, Reinsch N, Osada N, Wasmer K, Monnig G, Stypmann J, Breithardt G, Haverkamp W, Eckardt L: Verapamil prevents torsade de pointes by reduction of transmural dispersion of repolarization and suppression of early afterdepolarizations in an intact heart model of LQT3. Basic Res Cardiol. 2005 Jul;100(4):365-71. Epub 2005 Jun 10. [15944809 ]
General Function:
Voltage-gated calcium channel activity involved sa node cell action potential
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA).
Gene Name:
CACNA1D
Uniprot ID:
Q01668
Molecular Weight:
245138.75 Da
References
  1. Morgan EL, Mace OJ, Affleck J, Kellett GL: Apical GLUT2 and Cav1.3: regulation of rat intestinal glucose and calcium absorption. J Physiol. 2007 Apr 15;580(Pt. 2):593-604. Epub 2007 Feb 1. [17272350 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.
Gene Name:
CACNA1B
Uniprot ID:
Q00975
Molecular Weight:
262493.84 Da
References
  1. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. doi: 10.1111/j.1526-4610.2008.01298.x. [19125880 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by the funnel toxin (Ftx) and by the omega-agatoxin-IVA (omega-Aga-IVA). They are however insensitive to dihydropyridines (DHP), and omega-conotoxin-GVIA (omega-CTx-GVIA).
Gene Name:
CACNA1A
Uniprot ID:
O00555
Molecular Weight:
282362.39 Da
References
  1. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. doi: 10.1111/j.1526-4610.2008.01298.x. [19125880 ]