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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2022-03-07 02:51:58 UTC
HMDB IDHMDB0015374
Secondary Accession Numbers
  • HMDB15374
Metabolite Identification
Common NameBepridil
DescriptionBepridil is only found in individuals that have used or taken this drug. It is a long-acting calcium-blocking agent with significant anti-anginal activity. The drug produces significant coronary vasodilation and modest peripheral effects. It has antihypertensive and selective anti-arrhythmia activities and acts as a calmodulin antagonist. [PubChem]Bepridil has inhibitory effects on both the slow calcium (L-type) and fast sodium inward currents in myocardial and vascular smooth muscle, interferes with calcium binding to calmodulin, and blocks both voltage and receptor operated calcium channels. Bepridil inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. This has been demonstrated in isolated myocardial and vascular smooth muscle preparations in which both the slope of the calcium dose response curve and the maximum calcium-induced inotropic response were significantly reduced by bepridil. In cardiac myocytes in vitro, bepridil was shown to be tightly bound to actin. Bepridil regularly reduces heart rate and arterial pressure at rest and at a given level of exercise by dilating peripheral arterioles and reducing total peripheral resistance (afterload) against which the heart works.
Structure
Data?1582753289
Synonyms
ValueSource
BepadinChEBI
Bepridil, (+)-isomerHMDB
Bepridil, alpha-isomerHMDB
Monohydrochloride, bepridilHMDB
Riom brand OF bepridil hydrochlorideHMDB
VascorHMDB
1978 CERMHMDB
Bepridil monohydrochlorideHMDB
Bepridil monohydrochloride, monohydrateHMDB
Bepridil monohydrochloride, alpha isomerHMDB
Bepridil monohydrochloride, alpha-isomerHMDB
Bepridil, (-)-isomerHMDB
Bepridil, alpha isomerHMDB
CordiumHMDB
Wallace brand OF bepridil hydrochlorideHMDB
1978-CERMHMDB
Bepridil, (+-)-isomerHMDB
CERM-1978HMDB
BedapinHMDB
CERM 1978HMDB
Monohydrochloride, alpha-isomer bepridilHMDB
Nourypharma brand OF bepridil hydrochlorideHMDB
UnicordiumHMDB
Chemical FormulaC24H34N2O
Average Molecular Weight366.5396
Monoisotopic Molecular Weight366.26711372
IUPAC NameN-benzyl-N-[3-(2-methylpropoxy)-2-(pyrrolidin-1-yl)propyl]aniline
Traditional Namebepridil
CAS Registry Number64706-54-3
SMILES
CC(C)COCC(CN(CC1=CC=CC=C1)C1=CC=CC=C1)N1CCCC1
InChI Identifier
InChI=1S/C24H34N2O/c1-21(2)19-27-20-24(25-15-9-10-16-25)18-26(23-13-7-4-8-14-23)17-22-11-5-3-6-12-22/h3-8,11-14,21,24H,9-10,15-20H2,1-2H3
InChI KeyUIEATEWHFDRYRU-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as phenylbenzamines. These are aromatic compounds consisting of a benzyl group that is N-linked to a benzamine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylmethylamines
Direct ParentPhenylbenzamines
Alternative Parents
Substituents
  • Phenylbenzamine
  • Benzylamine
  • Tertiary aliphatic/aromatic amine
  • Aniline or substituted anilines
  • Dialkylarylamine
  • Aralkylamine
  • N-alkylpyrrolidine
  • Pyrrolidine
  • Tertiary amine
  • Tertiary aliphatic amine
  • Dialkyl ether
  • Ether
  • Azacycle
  • Organoheterocyclic compound
  • Organic oxygen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Physiological effectNot Available
Disposition
ProcessNot Available
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.0066 g/LNot Available
LogP5.2Not Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.0066 g/LALOGPS
logP5.33ALOGPS
logP5.49ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)9.16ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area15.71 ŲChemAxon
Rotatable Bond Count10ChemAxon
Refractivity115.12 m³·mol⁻¹ChemAxon
Polarizability43.5 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+188.02331661259
DarkChem[M-H]-186.13831661259
DeepCCS[M+H]+185.41130932474
DeepCCS[M-H]-183.05330932474
DeepCCS[M-2H]-216.85930932474
DeepCCS[M+Na]+192.20430932474
AllCCS[M+H]+192.932859911
AllCCS[M+H-H2O]+190.332859911
AllCCS[M+NH4]+195.332859911
AllCCS[M+Na]+196.032859911
AllCCS[M-H]-193.032859911
AllCCS[M+Na-2H]-193.332859911
AllCCS[M+HCOO]-193.832859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
BepridilCC(C)COCC(CN(CC1=CC=CC=C1)C1=CC=CC=C1)N1CCCC13349.7Standard polar33892256
BepridilCC(C)COCC(CN(CC1=CC=CC=C1)C1=CC=CC=C1)N1CCCC12675.8Standard non polar33892256
BepridilCC(C)COCC(CN(CC1=CC=CC=C1)C1=CC=CC=C1)N1CCCC12648.3Semi standard non polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Bepridil GC-MS (Non-derivatized) - 70eV, Positivesplash10-004m-8690000000-768d16d0b40d5b2932e72017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Bepridil GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Bepridil GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bepridil 10V, Positive-QTOFsplash10-066u-9327000000-af93fdc247abd705238e2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bepridil 20V, Positive-QTOFsplash10-0006-9320000000-2b4cc0379d6875c5c1ec2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bepridil 40V, Positive-QTOFsplash10-052f-9000000000-675ce98f6b729bc83dba2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bepridil 10V, Negative-QTOFsplash10-014i-2019000000-ad43d391dc0021d165212016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bepridil 20V, Negative-QTOFsplash10-05x0-8895000000-f6081c9498fdf024c1302016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bepridil 40V, Negative-QTOFsplash10-00di-9220000000-a3433671009f66e281062016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bepridil 10V, Positive-QTOFsplash10-014i-1309000000-d08b70c49dbd9bec8ecc2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bepridil 20V, Positive-QTOFsplash10-014l-9527000000-d456621f5de3ad386cb92021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bepridil 40V, Positive-QTOFsplash10-0006-9400000000-94c75315da72259763c82021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bepridil 10V, Negative-QTOFsplash10-014i-0219000000-f342a2f667dda5fca8272021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bepridil 20V, Negative-QTOFsplash10-07vi-3629000000-ebc015e4f6668c3775622021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bepridil 40V, Negative-QTOFsplash10-003r-9822000000-709fc32123a04540e60f2021-10-11Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01244 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01244 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01244
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2261
KEGG Compound IDC06847
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkBepridil
METLIN IDNot Available
PubChem Compound2351
PDB IDNot Available
ChEBI ID3061
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Only showing the first 10 proteins. There are 11 proteins in total.

Enzymes

General function:
Involved in catalytic activity
Specific function:
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a higher affinity for cGMP than for cAMP.
Gene Name:
PDE1A
Uniprot ID:
P54750
Molecular weight:
61251.38
References
  1. Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [PubMed:2933041 ]
General function:
Involved in catalytic activity
Specific function:
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a preference for cGMP as a substrate.
Gene Name:
PDE1B
Uniprot ID:
Q01064
Molecular weight:
61379.235
References
  1. Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [PubMed:2933041 ]
General function:
Involved in ATP binding
Specific function:
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
Gene Name:
ATP1A1
Uniprot ID:
P05023
Molecular weight:
112895.01
References
  1. Kovacic H, Gallice P, Crevat A: Inhibition of sodium pump by bepridil. An in vitro and microcalorimetric study. Biochem Pharmacol. 1992 Oct 20;44(8):1529-34. [PubMed:1329768 ]
  2. Raess BU, Record DM: Inhibition of erythrocyte Ca2(+)-pump by Ca2+ antagonists. Biochem Pharmacol. 1990 Dec 1;40(11):2549-55. [PubMed:2148481 ]
  3. Smith SJ, England PJ: The effects of reported Ca2+ sensitisers on the rates of Ca2+ release from cardiac troponin C and the troponin-tropomyosin complex. Br J Pharmacol. 1990 Aug;100(4):779-85. [PubMed:2207500 ]
  4. Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [PubMed:2933041 ]
  5. Fuchs J, Mainka L, Reifart N, Zimmer G: Effects of bepridil on heart mitochondrial membrane and the isolated rat heart preparation. Arzneimittelforschung. 1986 Feb;36(2):209-12. [PubMed:2938592 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in calcium ion binding
Specific function:
Calmodulin mediates the control of a large number of enzymes and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. Together with CEP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis
Gene Name:
CALM1
Uniprot ID:
P62158
Molecular weight:
16837.5
References
  1. Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [PubMed:2933041 ]
  2. Lamers JM, Verdouw PD, Mas-Oliva J: The effects of felodipine and bepridil on calcium-stimulated calmodulin binding and calcium pumping ATPase of cardiac sarcolemma before and after removal of endogenous calmodulin. Mol Cell Biochem. 1987 Dec;78(2):169-76. [PubMed:2964559 ]
General function:
Involved in ion channel activity
Specific function:
Probably important in cardiac repolarization. Associates with KCNE1 (MinK) to form the I(Ks) cardiac potassium current. Elicits a rapidly activating, potassium-selective outward current. Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current in CHO cells in which cloned KCNQ1/KCNE1 channels were coexpressed with M1 muscarinic receptors. May associate also with KCNE3 (MiRP2) to form the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions, which is reduced in cystic fibrosis and pathologically stimulated in cholera and other forms of secretory diarrhea
Gene Name:
KCNQ1
Uniprot ID:
P51787
Molecular weight:
74697.9
References
  1. Chouabe C, Drici MD, Romey G, Barhanin J: Effects of calcium channel blockers on cloned cardiac K+ channels IKr and IKs. Therapie. 2000 Jan-Feb;55(1):195-202. [PubMed:10860024 ]
  2. Yumoto Y, Horie M, Kubota T, Ninomiya T, Kobori A, Takenaka K, Takano M, Niwano S, Izumi T: Bepridil block of recombinant human cardiac IKs current shows a time-dependent unblock. J Cardiovasc Pharmacol. 2004 Feb;43(2):178-82. [PubMed:14716203 ]
  3. Chouabe C, Drici MD, Romey G, Barhanin J, Lazdunski M: HERG and KvLQT1/IsK, the cardiac K+ channels involved in long QT syndromes, are targets for calcium channel blockers. Mol Pharmacol. 1998 Oct;54(4):695-703. [PubMed:9765513 ]
General function:
Involved in calcium channel activity
Specific function:
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G). Overexpression induces apoptosis
Gene Name:
CACNA2D2
Uniprot ID:
Q9NY47
Molecular weight:
129875.2
References
  1. Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [PubMed:1281221 ]
  2. Bezprozvanny I, Tsien RW: Voltage-dependent blockade of diverse types of voltage-gated Ca2+ channels expressed in Xenopus oocytes by the Ca2+ channel antagonist mibefradil (Ro 40-5967). Mol Pharmacol. 1995 Sep;48(3):540-9. [PubMed:7565636 ]
General function:
Involved in ion 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:
282362.4
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. [PubMed: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. [PubMed:17016423 ]
  3. Bezprozvanny I, Tsien RW: Voltage-dependent blockade of diverse types of voltage-gated Ca2+ channels expressed in Xenopus oocytes by the Ca2+ channel antagonist mibefradil (Ro 40-5967). Mol Pharmacol. 1995 Sep;48(3):540-9. [PubMed:7565636 ]
General function:
Involved in ion 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-1H 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
Gene Name:
CACNA1H
Uniprot ID:
O95180
Molecular weight:
259160.2
References
  1. Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [PubMed:1281221 ]
  2. Bezprozvanny I, Tsien RW: Voltage-dependent blockade of diverse types of voltage-gated Ca2+ channels expressed in Xenopus oocytes by the Ca2+ channel antagonist mibefradil (Ro 40-5967). Mol Pharmacol. 1995 Sep;48(3):540-9. [PubMed:7565636 ]
General function:
Involved in calcium ion binding
Specific function:
Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components:Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments
Gene Name:
TNNC1
Uniprot ID:
P63316
Molecular weight:
18402.4
References
  1. Abusamhadneh E, Abbott MB, Dvoretsky A, Finley N, Sasi S, Rosevear PR: Interaction of bepridil with the cardiac troponin C/troponin I complex. FEBS Lett. 2001 Sep 28;506(1):51-4. [PubMed:11591369 ]
  2. Wang X, Li MX, Sykes BD: Structure of the regulatory N-domain of human cardiac troponin C in complex with human cardiac troponin I147-163 and bepridil. J Biol Chem. 2002 Aug 23;277(34):31124-33. Epub 2002 Jun 11. [PubMed:12060657 ]
  3. MacLachlan LK, Reid DG, Mitchell RC, Salter CJ, Smith SJ: Binding of a calcium sensitizer, bepridil, to cardiac troponin C. A fluorescence stopped-flow kinetic, circular dichroism, and proton nuclear magnetic resonance study. J Biol Chem. 1990 Jun 15;265(17):9764-70. [PubMed:2351672 ]
  4. Kleerekoper Q, Liu W, Choi D, Putkey JA: Identification of binding sites for bepridil and trifluoperazine on cardiac troponin C. J Biol Chem. 1998 Apr 3;273(14):8153-60. [PubMed:9525919 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Ibrahim S, Peggins J, Knapton A, Licht T, Aszalos A: Influence of antipsychotic, antiemetic, and Ca(2+) channel blocker drugs on the cellular accumulation of the anticancer drug daunorubicin: P-glycoprotein modulation. J Pharmacol Exp Ther. 2000 Dec;295(3):1276-83. [PubMed:11082465 ]

Only showing the first 10 proteins. There are 11 proteins in total.