Bepridil
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Bepridil
- DrugBank Accession Number
- DB01244
- Background
A long-acting, non selective, calcium channel blocker 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. It is no longer marketed in the United States, as it has been implicated in causing ventricular arrhythmias (ie. Torsade de pointes).
- Type
- Small Molecule
- Groups
- Approved, Withdrawn
- Structure
- Weight
- Average: 366.5396
Monoisotopic: 366.26711372 - Chemical Formula
- C24H34N2O
- Synonyms
- 1-(2-(N-BENZYLANILINO)-1-(ISOBUTOXYMETHYL)ETHYL)-PYRROLIDINE
- 1-PYRROLIDENEETHANAMINE, .BETA.-((2-METHYLPROPOXY)METHYL)-N-PHENYL-N-(PHENYLMETHYL)-
- Bepadin
- Bepridil
- External IDs
- Org 5730
Pharmacology
- Indication
For the treatment of hypertension, and chronic stable angina (classic effort-associated angina).
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- Pharmacodynamics
Bepridil is a calcium channel blocker that has well characterized anti-anginal properties and known but poorly characterized type 1 anti-arrhythmic and anti-hypertensive properties. It is not related chemically to other calcium channel blockers such as diltiazem hydrochloride, nifedipine and verapamil hydrochloride.
- Mechanism of action
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.
Target Actions Organism AVoltage-dependent P/Q-type calcium channel subunit alpha-1A inhibitorHumans AVoltage-dependent T-type calcium channel subunit alpha-1H inhibitorHumans AVoltage-dependent calcium channel subunit alpha-2/delta-2 inhibitorHumans USodium/potassium-transporting ATPase subunit alpha-1 inhibitorHumans UPotassium voltage-gated channel subfamily KQT member 1 inhibitorHumans UTroponin C, slow skeletal and cardiac muscles otherHumans UDual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B inhibitorHumans UDual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A inhibitorHumans UVoltage-gated inwardly rectifying potassium channel KCNH2 inhibitorHumans UCalmodulin binderHumans - Absorption
Rapidly and completely absorbed after oral administration.
- Volume of distribution
Not Available
- Protein binding
99%
- Metabolism
Hepatic.
- Route of elimination
Not Available
- Half-life
24-50 hours
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
There has been one experience with overdosage in which a patient inadvertently took a single dose of 1600 mg of bepridil. The patient was observed for 72 hours in intensive care, but no significant adverse experiences were noted.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbaloparatide The risk or severity of adverse effects can be increased when Bepridil is combined with Abaloparatide. Abametapir The serum concentration of Bepridil can be increased when it is combined with Abametapir. Abatacept The metabolism of Bepridil can be increased when combined with Abatacept. Abiraterone The metabolism of Bepridil can be decreased when combined with Abiraterone. Acarbose The risk or severity of hypoglycemia can be increased when Bepridil is combined with Acarbose. - Food Interactions
- Avoid alcohol. Alcohol can potentiate hypotension and dizziness when taken with this drug.
- Take with food. Food reduces nausea.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Bepridil hydrochloride 4W2P15D93M 74764-40-2 UEECHQPWQHYEDE-UHFFFAOYSA-N Bepridil hydrochloride anhydrous 2TN7FF3W4M 68099-86-5 JXBBWYGMTNAYNM-UHFFFAOYSA-N - International/Other Brands
- Angopril / Cordium / Vascor
Categories
- ATC Codes
- C08EA02 — Bepridil
- Drug Categories
- Agents causing hyperkalemia
- Antiarrhythmic agents
- Antihypertensive Agents
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Calcium-Regulating Hormones and Agents
- Cardiovascular Agents
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Highest Risk QTc-Prolonging Agents
- Hypotensive Agents
- Membrane Transport Modulators
- Non-Selective Calcium Channel Blockers
- P-glycoprotein inhibitors
- Phenylalkylamine Derivatives
- Pyrrolidines
- QTc Prolonging Agents
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound 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.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Phenylmethylamines
- Direct Parent
- Phenylbenzamines
- Alternative Parents
- Dialkylarylamines / Benzylamines / Aniline and substituted anilines / Aralkylamines / N-alkylpyrrolidines / Trialkylamines / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Amine / Aniline or substituted anilines / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Benzylamine / Dialkyl ether / Dialkylarylamine / Ether / Hydrocarbon derivative
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- tertiary amine, pyrrolidines (CHEBI:3061)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 755BO701MA
- CAS number
- 64706-54-3
- InChI Key
- UIEATEWHFDRYRU-UHFFFAOYSA-N
- InChI
- 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
- IUPAC Name
- N-benzyl-N-[3-(2-methylpropoxy)-2-(pyrrolidin-1-yl)propyl]aniline
- SMILES
- CC(C)COCC(CN(CC1=CC=CC=C1)C1=CC=CC=C1)N1CCCC1
References
- Synthesis Reference
Mauvernay, R.Y., Busch, N., Moleyre, J., Monteil, A. and Simond, J.; U.S. Patent 3,962,238; June 8,1976; assigned to Centre Europeen de Recherches Mauvernay "CERM".
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015374
- KEGG Drug
- D07520
- KEGG Compound
- C06847
- PubChem Compound
- 2351
- PubChem Substance
- 46506353
- ChemSpider
- 2261
- BindingDB
- 78577
- 1436
- ChEBI
- 3061
- ChEMBL
- CHEMBL1008
- Therapeutic Targets Database
- DAP000525
- PharmGKB
- PA164754755
- Guide to Pharmacology
- GtP Drug Page
- PDBe Ligand
- BEP
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Bepridil
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 128 Mauvernay, R.Y., Busch, N., Moleyre, J., Monteil, A. and Simond, J.; U.S. Patent 3,962,238; June 8,1976; assigned to Centre Europeen de Recherches Mauvernay "CERM". water solubility Slightly soluble Not Available logP 5.2 Not Available - Predicted Properties
Property Value Source Water Solubility 0.00655 mg/mL ALOGPS logP 5.33 ALOGPS logP 5.49 Chemaxon logS -4.8 ALOGPS pKa (Strongest Basic) 9.16 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 15.71 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 115.12 m3·mol-1 Chemaxon Polarizability 43.5 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9859 Blood Brain Barrier + 0.9003 Caco-2 permeable + 0.5593 P-glycoprotein substrate Substrate 0.7013 P-glycoprotein inhibitor I Inhibitor 0.7951 P-glycoprotein inhibitor II Inhibitor 0.8387 Renal organic cation transporter Inhibitor 0.6774 CYP450 2C9 substrate Non-substrate 0.7898 CYP450 2D6 substrate Non-substrate 0.9117 CYP450 3A4 substrate Substrate 0.5495 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Inhibitor 0.8932 CYP450 2C19 inhibitor Inhibitor 0.8994 CYP450 3A4 inhibitor Non-inhibitor 0.8462 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5636 Ames test Non AMES toxic 0.67 Carcinogenicity Non-carcinogens 0.8688 Biodegradation Not ready biodegradable 0.9938 Rat acute toxicity 2.4903 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.536 hERG inhibition (predictor II) Inhibitor 0.796
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-004m-8690000000-768d16d0b40d5b2932e7 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-1509000000-635c2b439fcbf1756246 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-5819000000-2b77629c8a446a4f872b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-096u-9535000000-b33fb61876bbc8b56484 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0gb9-3897000000-1eac5e948a946ed42392 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-08fu-7911000000-f8f867cc8c3890f624e2 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0udl-5921000000-5a9dce6c764aec7589a1 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 206.4348802 predictedDarkChem Lite v0.1.0 [M-H]- 183.05354 predictedDeepCCS 1.0 (2019) [M+H]+ 207.3563802 predictedDarkChem Lite v0.1.0 [M+H]+ 185.41151 predictedDeepCCS 1.0 (2019) [M+Na]+ 207.9841802 predictedDarkChem Lite v0.1.0 [M+Na]+ 192.20418 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 specifically blocked by the spider omega-agatoxin-IVA (AC P54282) (By similarity). They are however insensitive to dihydropyridines (DHP)
- Specific Function
- amyloid-beta binding
- Gene Name
- CACNA1A
- Uniprot ID
- O00555
- Uniprot Name
- Voltage-dependent P/Q-type calcium channel subunit alpha-1A
- Molecular Weight
- 282561.605 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Voltage-sensitive calcium channel that gives rise to T-type calcium currents. T-type calcium channels belong to the 'low-voltage activated (LVA)' group. A particularity of this type of channel is an opening at quite negative potentials, and a voltage-dependent inactivation (PubMed:27149520, PubMed:9670923, PubMed:9930755). 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 (Probable). They may also be involved in the modulation of firing patterns of neurons (PubMed:15048902). In the adrenal zona glomerulosa, participates in the signaling pathway leading to aldosterone production in response to either AGT/angiotensin II, or hyperkalemia (PubMed:25907736, PubMed:27729216)
- Specific Function
- high voltage-gated calcium channel activity
- Gene Name
- CACNA1H
- Uniprot ID
- O95180
- Uniprot Name
- Voltage-dependent T-type calcium channel subunit alpha-1H
- Molecular Weight
- 259160.2 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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) (PubMed:15111129, PubMed:23339110). Overexpression induces apoptosis
- Specific Function
- metal ion binding
- Gene Name
- CACNA2D2
- Uniprot ID
- Q9NY47
- Uniprot Name
- Voltage-dependent calcium channel subunit alpha-2/delta-2
- Molecular Weight
- 129816.095 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General 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 (PubMed:29499166, PubMed:30388404). Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis (By similarity)
- Specific Function
- ATP binding
- Gene Name
- ATP1A1
- Uniprot ID
- P05023
- Uniprot Name
- Sodium/potassium-transporting ATPase subunit alpha-1
- Molecular Weight
- 112895.01 Da
References
- 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. [Article]
- Raess BU, Record DM: Inhibition of erythrocyte Ca2(+)-pump by Ca2+ antagonists. Biochem Pharmacol. 1990 Dec 1;40(11):2549-55. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (PubMed:10646604, PubMed:25441029). Associates with KCNE beta subunits that modulates current kinetics (PubMed:10646604, PubMed:11101505, PubMed:19687231, PubMed:8900283, PubMed:9108097, PubMed:9312006). Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current (PubMed:10646604, PubMed:11101505, PubMed:25441029, PubMed:8900283, PubMed:9108097, PubMed:9312006). Promotes also a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:10646604, PubMed:11101505, PubMed:8900283, PubMed:9108097, PubMed:9312006). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5-bisphosphate (PubMed:25037568). KCNQ1-KCNE2 channel associates with Na(+)-coupled myo-inositol symporter in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability
- Specific Function
- calmodulin binding
- Gene Name
- KCNQ1
- Uniprot ID
- P51787
- Uniprot Name
- Potassium voltage-gated channel subfamily KQT member 1
- Molecular Weight
- 74697.925 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Other
- General 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
- Specific Function
- actin filament binding
- Gene Name
- TNNC1
- Uniprot ID
- P63316
- Uniprot Name
- Troponin C, slow skeletal and cardiac muscles
- Molecular Weight
- 18402.36 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:15260978, PubMed:8855339, PubMed:9419816). Has a preference for cGMP as a substrate (PubMed:9419816)
- Specific Function
- 3',5'-cyclic-AMP phosphodiesterase activity
- Gene Name
- PDE1B
- Uniprot ID
- Q01064
- Uniprot Name
- Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B
- Molecular Weight
- 61379.235 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Calcium/calmodulin-dependent cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cGMP and cAMP, which are key regulators of many important physiological processes. Has a higher efficiency with cGMP compared to cAMP
- Specific Function
- calmodulin binding
- Gene Name
- PDE1A
- Uniprot ID
- P54750
- Uniprot Name
- Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A
- Molecular Weight
- 61251.38 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Characterized by unusual gating kinetics by producing relatively small outward currents during membrane depolarization and large inward currents during subsequent repolarization which reflect a rapid inactivation during depolarization and quick recovery from inactivation but slow deactivation (closing) during repolarization (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Forms a stable complex with KCNE1 or KCNE2, and that this heteromultimerization regulates inward rectifier potassium channel activity (PubMed:10219239, PubMed:9230439)
- Specific Function
- delayed rectifier potassium channel activity
- Gene Name
- KCNH2
- Uniprot ID
- Q12809
- Uniprot Name
- Voltage-gated inwardly rectifying potassium channel KCNH2
- Molecular Weight
- 126653.52 Da
References
- Chiu PJ, Marcoe KF, Bounds SE, Lin CH, Feng JJ, Lin A, Cheng FC, Crumb WJ, Mitchell R: Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels. J Pharmacol Sci. 2004 Jul;95(3):311-9. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding (PubMed:16760425, PubMed:23893133, PubMed:26969752, PubMed:27165696, PubMed:28890335, PubMed:31454269, PubMed:35568036). Calcium-binding is required for the activation of calmodulin (PubMed:16760425, PubMed:23893133, PubMed:26969752, PubMed:27165696, PubMed:28890335, PubMed:31454269, PubMed:35568036). Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases (PubMed:16760425, PubMed:23893133, PubMed:26969752, PubMed:27165696, PubMed:28890335, PubMed:31454269, PubMed:35568036). Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Is a regulator of voltage-dependent L-type calcium channels (PubMed:31454269). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696). Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding (PubMed:25441029). Acts as a sensor to modulate the endoplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2 (PubMed:28890335)
- Specific Function
- adenylate cyclase activator activity
Components:
Name | UniProt ID |
---|---|
Calmodulin-1 | P0DP23 |
Calmodulin-2 | P0DP24 |
Calmodulin-3 | P0DP25 |
References
- 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. [Article]
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Doki K, Sekiguchi Y, Kuga K, Aonuma K, Homma M: Serum flecainide S/R ratio reflects the CYP2D6 genotype and changes in CYP2D6 activity. Drug Metab Pharmacokinet. 2015 Aug;30(4):257-62. doi: 10.1016/j.dmpk.2015.04.001. Epub 2015 Apr 11. [Article]
- Taguchi M, Fujiki A, Iwamoto J, Inoue H, Tahara K, Saigusa K, Horiuchi I, Oshima Y, Hashimoto Y: Nonlinear mixed effects model analysis of the pharmacokinetics of routinely administered bepridil in Japanese patients with arrhythmias. Biol Pharm Bull. 2006 Mar;29(3):517-21. doi: 10.1248/bpb.29.517. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Uesawa Y, Takeuchi T, Mohri K: Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 29, 2024 18:22