Identification
- Generic Name
- Mibefradil
- DrugBank Accession Number
- DB01388
- Background
Mibefradil was withdrawn from the market in 1998 because of potentially harmful interactions with other drugs.
- Type
- Small Molecule
- Groups
- Investigational, Withdrawn
- Structure
Structure for Mibefradil (DB01388)
- Weight
- Average: 495.6287
Monoisotopic: 495.289720302 - Chemical Formula
- C29H38FN3O3
- Synonyms
- Mibefradil
- External IDs
- RO 40-5967
Pharmacology
- Indication
For the treatment of angina and high blood pressure.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Mibefradil belongs to a group of medicines called calcium channel blocking agents, or, more commonly, calcium channel blockers. Calcium channel blocking agents affect the movement of calcium into the cells of the heart and blood vessels. As a result, they relax blood vessels and increase the supply of blood and oxygen to the heart while reducing its workload. Mibefradil is a benzimidazoyl-substituted tetraline that selectively binds and inhibits T-type calcium channels.
- Mechanism of action
Mibefradil is a tetralol calcium channel blocking agent that inhibits the influx of calcium ions across both the T (low-voltage) and L (high-voltage) calcium channels of cardiac and vascular smooth muscle, with a greater selectivity for T channels. Vasodilation occurs in vascular smooth muscle, causing a decrease in peripheral vascular resistance and a resulting decrease in blood pressure. Mibefradil causes a slight increase in cardiac output during chronic dosing. Mibefradil slows sinus and atrioventricular (AV) node conduction, producing a slight reduction in heart rate and a slight increase in the PR interval. It has also been shown to slightly lengthen the corrected sinus node recovery time and AH interval and to raise the Wenckebach point. The mechanism by which mibefradil reduces angina is not known, but is thought to be attributed to a reduction in heart rate, total peripheral resistance (afterload), and the heart rate–systolic blood pressure product at any given level of exercise. The result of these effects is a decrease in cardiac workload and myocardial oxygen demand.
Target Actions Organism AVoltage-dependent T-type calcium channel subunit alpha-1G inhibitorHumans AVoltage-dependent T-type calcium channel subunit alpha-1H inhibitorHumans AVoltage-dependent L-type calcium channel subunit alpha-1C inhibitorHumans AVoltage-dependent L-type calcium channel subunit alpha-1D inhibitorHumans AVoltage-dependent L-type calcium channel subunit alpha-1F inhibitorHumans AVoltage-dependent T-type calcium channel subunit alpha-1I inhibitorHumans AVoltage-dependent L-type calcium channel subunit alpha-1S inhibitorHumans AVoltage-dependent L-type calcium channel subunit beta-1 inhibitorHumans AVoltage-dependent L-type calcium channel subunit beta-2 inhibitorHumans AVoltage-dependent L-type calcium channel subunit beta-3 inhibitorHumans AVoltage-dependent L-type calcium channel subunit beta-4 inhibitorHumans - Absorption
Bioavailability after a single dose is 70%. After multiple dosing, the proportion of mibefradil undergoing first-pass metabolism is reduced, resulting in a steady state bioavailability of approximately 90%. Food does not affect the rate or extent of absorption of mibefradil.
- Volume of distribution
Not Available
- Protein binding
≥ 99%, primarily to alpha 1-acid glycoprotein.
- Metabolism
The two metabolic pathways that mibefradil undergoes are esterase-catalyzed hydrolysis of the ester side chain (producing an alcohol metabolite) and cytochrome P450 3A4-catalyzed oxidation (that becomes less important during chronic dosing). The pharmacologic effect of the metabolite is approximately 10% of that of the parent mibefradil.
- Route of elimination
Not Available
- Half-life
17 to 25 hours at steady state.
- 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
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 Abaloparatide may increase the hypotensive activities of Mibefradil. Abametapir The serum concentration of Mibefradil can be increased when it is combined with Abametapir. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Mibefradil. Abrocitinib The serum concentration of Mibefradil can be increased when it is combined with Abrocitinib. Acalabrutinib The serum concentration of Acalabrutinib can be increased when it is combined with Mibefradil. - Food Interactions
- Not Available
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 Mibefradil Dihydrochloride 842TUP3PQ8 116666-63-8 MTJLQTFHJIHXIX-GDUXWEAWSA-N - International/Other Brands
- Batenac (Solvay Pharma) / Befral (Orion) / Cerate (Asta Medica) / Posicor (Roche) / Quota / Taxben (Berenguer Infale)
Categories
- ATC Codes
- C08CX01 — Mibefradil
- Drug Categories
- Agents causing hyperkalemia
- Antiarrhythmic agents
- Antihypertensive Agents
- Benzimidazoles
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Calcium-Regulating Hormones and Agents
- Cardiovascular Agents
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Inhibitors
- Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A7 Inhibitors
- Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Membrane Transport Modulators
- Moderate Risk QTc-Prolonging Agents
- Naphthalenes
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- QTc Prolonging Agents
- Selective Calcium Channel Blockers With Mainly Vascular Effects
- Tetrahydronaphthalenes
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as tetralins. These are polycyclic aromatic compounds containing a tetralin moiety, which consists of a benzene fused to a cyclohexane.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Tetralins
- Sub Class
- Not Available
- Direct Parent
- Tetralins
- Alternative Parents
- Benzimidazoles / Aralkylamines / Aryl fluorides / Heteroaromatic compounds / Imidazoles / Trialkylamines / Amino acids and derivatives / Carboxylic acid esters / Dialkyl ethers / Azacyclic compounds show 6 more
- Substituents
- Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Azole / Benzimidazole / Carbonyl group show 20 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- tetralins (CHEBI:6920)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 27B90X776A
- CAS number
- 116644-53-2
- InChI Key
- HBNPJJILLOYFJU-VMPREFPWSA-N
- InChI
- InChI=1S/C29H38FN3O3/c1-20(2)28-23-12-11-22(30)18-21(23)13-14-29(28,36-27(34)19-35-4)15-17-33(3)16-7-10-26-31-24-8-5-6-9-25(24)32-26/h5-6,8-9,11-12,18,20,28H,7,10,13-17,19H2,1-4H3,(H,31,32)/t28-,29-/m0/s1
- IUPAC Name
- (1S,2S)-2-(2-{[3-(1H-1,3-benzodiazol-2-yl)propyl](methyl)amino}ethyl)-6-fluoro-1-(propan-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl 2-methoxyacetate
- SMILES
- COCC(=O)O[C@]1(CCN(C)CCCC2=NC3=CC=CC=C3N2)CCC2=C(C=CC(F)=C2)[C@@H]1C(C)C
References
- General References
- Not Available
- External Links
- KEGG Compound
- C07222
- PubChem Compound
- 60663
- PubChem Substance
- 46504498
- ChemSpider
- 54673
- BindingDB
- 78934
- 83213
- ChEBI
- 6920
- ChEMBL
- CHEMBL45816
- ZINC
- ZINC000003782486
- Therapeutic Targets Database
- DCL000341
- PharmGKB
- PA450492
- PDBe Ligand
- MWV
- Wikipedia
- Mibefradil
- PDB Entries
- 6oo9 / 7wlj
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 1 Completed Treatment Brain and Central Nervous System Tumors 1 1 Completed Treatment Glioblastoma Multiforme (GBM) 1 1 Completed Treatment Healthy Subjects (HS) 1
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 Caco2 permeability -4.87 ADME Research, USCD - Predicted Properties
Property Value Source Water Solubility 0.00104 mg/mL ALOGPS logP 5.34 ALOGPS logP 5.16 Chemaxon logS -5.7 ALOGPS pKa (Strongest Acidic) 12.54 Chemaxon pKa (Strongest Basic) 9.82 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 67.45 Å2 Chemaxon Rotatable Bond Count 12 Chemaxon Refractivity 139.73 m3·mol-1 Chemaxon Polarizability 55.34 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9964 Blood Brain Barrier + 0.5 Caco-2 permeable + 0.5 P-glycoprotein substrate Substrate 0.9087 P-glycoprotein inhibitor I Inhibitor 0.8718 P-glycoprotein inhibitor II Inhibitor 0.8388 Renal organic cation transporter Non-inhibitor 0.549 CYP450 2C9 substrate Non-substrate 0.8596 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.7408 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Inhibitor 0.8932 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Inhibitor 0.796 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6921 Ames test Non AMES toxic 0.6864 Carcinogenicity Non-carcinogens 0.892 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.8610 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9611 hERG inhibition (predictor II) Inhibitor 0.7742
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0000900000-200ec98963eeb5d0c24b Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0gvo-2000900000-4bbc5203c251a273f202 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0pb9-0231900000-30204752d080521c2fdb Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00dr-9100200000-c7fe7a0fb8f7a704f11b Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-3904100000-100383a1c72759d1ab30 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-003b-1961300000-b3744cdd6ba1d7cd78e2 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]- 215.08519 predictedDeepCCS 1.0 (2019) [M+H]+ 217.48077 predictedDeepCCS 1.0 (2019) [M+Na]+ 223.3933 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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, hor...
- Gene Name
- CACNA1G
- Uniprot ID
- O43497
- Uniprot Name
- Voltage-dependent T-type calcium channel subunit alpha-1G
- Molecular Weight
- 262468.62 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Lee TS, Kaku T, Takebayashi S, Uchino T, Miyamoto S, Hadama T, Perez-Reyes E, Ono K: Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms. Pharmacology. 2006;78(1):11-20. Epub 2006 Aug 7. [Article]
- Monteil A, Chemin J, Bourinet E, Mennessier G, Lory P, Nargeot J: Molecular and functional properties of the human alpha(1G) subunit that forms T-type calcium channels. J Biol Chem. 2000 Mar 3;275(9):6090-100. [Article]
- Massie BM: Mibefradil: a selective T-type calcium antagonist. Am J Cardiol. 1997 Nov 6;80(9A):23I-32I. [Article]
- Clozel JP, Ertel EA, Ertel SI: Discovery and main pharmacological properties of mibefradil (Ro 40-5967), the first selective T-type calcium channel blocker. J Hypertens Suppl. 1997 Dec;15(5):S17-25. [Article]
- McNulty MM, Hanck DA: State-dependent mibefradil block of Na+ channels. Mol Pharmacol. 2004 Dec;66(6):1652-61. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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, hor...
- Gene Name
- CACNA1H
- Uniprot ID
- O95180
- Uniprot Name
- Voltage-dependent T-type calcium channel subunit alpha-1H
- Molecular Weight
- 259160.2 Da
References
- Brueggemann LI, Martin BL, Barakat J, Byron KL, Cribbs LL: Low voltage-activated calcium channels in vascular smooth muscle: T-type channels and AVP-stimulated calcium spiking. Am J Physiol Heart Circ Physiol. 2005 Feb;288(2):H923-35. Epub 2004 Oct 21. [Article]
- Coste B, Crest M, Delmas P: Pharmacological dissection and distribution of NaN/Nav1.9, T-type Ca2+ currents, and mechanically activated cation currents in different populations of DRG neurons. J Gen Physiol. 2007 Jan;129(1):57-77. [Article]
- Cribbs LL, Lee JH, Yang J, Satin J, Zhang Y, Daud A, Barclay J, Williamson MP, Fox M, Rees M, Perez-Reyes E: Cloning and characterization of alpha1H from human heart, a member of the T-type Ca2+ channel gene family. Circ Res. 1998 Jul 13;83(1):103-9. [Article]
- Lee TS, Kaku T, Takebayashi S, Uchino T, Miyamoto S, Hadama T, Perez-Reyes E, Ono K: Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms. Pharmacology. 2006;78(1):11-20. Epub 2006 Aug 7. [Article]
- Perez-Reyes E: Paradoxical role of T-type calcium channels in coronary smooth muscle. Mol Interv. 2004 Feb;4(1):16-8. [Article]
- Massie BM: Mibefradil: a selective T-type calcium antagonist. Am J Cardiol. 1997 Nov 6;80(9A):23I-32I. [Article]
- Clozel JP, Ertel EA, Ertel SI: Discovery and main pharmacological properties of mibefradil (Ro 40-5967), the first selective T-type calcium channel blocker. J Hypertens Suppl. 1997 Dec;15(5):S17-25. [Article]
- McNulty MM, Hanck DA: State-dependent mibefradil block of Na+ channels. Mol Pharmacol. 2004 Dec;66(6):1652-61. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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, hor...
- Gene Name
- CACNA1C
- Uniprot ID
- Q13936
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit alpha-1C
- Molecular Weight
- 248974.1 Da
References
- Moosmang S, Haider N, Bruderl B, Welling A, Hofmann F: Antihypertensive effects of the putative T-type calcium channel antagonist mibefradil are mediated by the L-type calcium channel Cav1.2. Circ Res. 2006 Jan 6;98(1):105-10. Epub 2005 Nov 23. [Article]
- Lee TS, Kaku T, Takebayashi S, Uchino T, Miyamoto S, Hadama T, Perez-Reyes E, Ono K: Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms. Pharmacology. 2006;78(1):11-20. Epub 2006 Aug 7. [Article]
- Mocanu MM, Gadgil S, Yellon DM, Baxter GF: Mibefradil, a T-type and L-type calcium channel blocker, limits infarct size through a glibenclamide-sensitive mechanism. Cardiovasc Drugs Ther. 1999 Apr;13(2):115-22. [Article]
- Jimenez C, Bourinet E, Leuranguer V, Richard S, Snutch TP, Nargeot J: Determinants of voltage-dependent inactivation affect Mibefradil block of calcium channels. Neuropharmacology. 2000;39(1):1-10. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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, hor...
- Gene Name
- CACNA1D
- Uniprot ID
- Q01668
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit alpha-1D
- Molecular Weight
- 245138.75 Da
References
- Mocanu MM, Gadgil S, Yellon DM, Baxter GF: Mibefradil, a T-type and L-type calcium channel blocker, limits infarct size through a glibenclamide-sensitive mechanism. Cardiovasc Drugs Ther. 1999 Apr;13(2):115-22. [Article]
- Jimenez C, Bourinet E, Leuranguer V, Richard S, Snutch TP, Nargeot J: Determinants of voltage-dependent inactivation affect Mibefradil block of calcium channels. Neuropharmacology. 2000;39(1):1-10. [Article]
- Lee TS, Kaku T, Takebayashi S, Uchino T, Miyamoto S, Hadama T, Perez-Reyes E, Ono K: Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms. Pharmacology. 2006;78(1):11-20. Epub 2006 Aug 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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, hor...
- Gene Name
- CACNA1F
- Uniprot ID
- O60840
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit alpha-1F
- Molecular Weight
- 220675.9 Da
References
- Mocanu MM, Gadgil S, Yellon DM, Baxter GF: Mibefradil, a T-type and L-type calcium channel blocker, limits infarct size through a glibenclamide-sensitive mechanism. Cardiovasc Drugs Ther. 1999 Apr;13(2):115-22. [Article]
- Jimenez C, Bourinet E, Leuranguer V, Richard S, Snutch TP, Nargeot J: Determinants of voltage-dependent inactivation affect Mibefradil block of calcium channels. Neuropharmacology. 2000;39(1):1-10. [Article]
- Lee TS, Kaku T, Takebayashi S, Uchino T, Miyamoto S, Hadama T, Perez-Reyes E, Ono K: Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms. Pharmacology. 2006;78(1):11-20. Epub 2006 Aug 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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, hor...
- Gene Name
- CACNA1I
- Uniprot ID
- Q9P0X4
- Uniprot Name
- Voltage-dependent T-type calcium channel subunit alpha-1I
- Molecular Weight
- 245100.8 Da
References
- Massie BM: Mibefradil: a selective T-type calcium antagonist. Am J Cardiol. 1997 Nov 6;80(9A):23I-32I. [Article]
- Clozel JP, Ertel EA, Ertel SI: Discovery and main pharmacological properties of mibefradil (Ro 40-5967), the first selective T-type calcium channel blocker. J Hypertens Suppl. 1997 Dec;15(5):S17-25. [Article]
- McNulty MM, Hanck DA: State-dependent mibefradil block of Na+ channels. Mol Pharmacol. 2004 Dec;66(6):1652-61. [Article]
- Lee TS, Kaku T, Takebayashi S, Uchino T, Miyamoto S, Hadama T, Perez-Reyes E, Ono K: Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms. Pharmacology. 2006;78(1):11-20. Epub 2006 Aug 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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, hor...
- Gene Name
- CACNA1S
- Uniprot ID
- Q13698
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit alpha-1S
- Molecular Weight
- 212348.1 Da
References
- Mocanu MM, Gadgil S, Yellon DM, Baxter GF: Mibefradil, a T-type and L-type calcium channel blocker, limits infarct size through a glibenclamide-sensitive mechanism. Cardiovasc Drugs Ther. 1999 Apr;13(2):115-22. [Article]
- Jimenez C, Bourinet E, Leuranguer V, Richard S, Snutch TP, Nargeot J: Determinants of voltage-dependent inactivation affect Mibefradil block of calcium channels. Neuropharmacology. 2000;39(1):1-10. [Article]
- Lee TS, Kaku T, Takebayashi S, Uchino T, Miyamoto S, Hadama T, Perez-Reyes E, Ono K: Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms. Pharmacology. 2006;78(1):11-20. Epub 2006 Aug 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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 ina...
- Gene Name
- CACNB1
- Uniprot ID
- Q02641
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit beta-1
- Molecular Weight
- 65712.995 Da
References
- Lee TS, Kaku T, Takebayashi S, Uchino T, Miyamoto S, Hadama T, Perez-Reyes E, Ono K: Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms. Pharmacology. 2006;78(1):11-20. Epub 2006 Aug 7. [Article]
- Mocanu MM, Gadgil S, Yellon DM, Baxter GF: Mibefradil, a T-type and L-type calcium channel blocker, limits infarct size through a glibenclamide-sensitive mechanism. Cardiovasc Drugs Ther. 1999 Apr;13(2):115-22. [Article]
- Jimenez C, Bourinet E, Leuranguer V, Richard S, Snutch TP, Nargeot J: Determinants of voltage-dependent inactivation affect Mibefradil block of calcium channels. Neuropharmacology. 2000;39(1):1-10. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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 ina...
- Gene Name
- CACNB2
- Uniprot ID
- Q08289
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit beta-2
- Molecular Weight
- 73579.925 Da
References
- Lee TS, Kaku T, Takebayashi S, Uchino T, Miyamoto S, Hadama T, Perez-Reyes E, Ono K: Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms. Pharmacology. 2006;78(1):11-20. Epub 2006 Aug 7. [Article]
- Mocanu MM, Gadgil S, Yellon DM, Baxter GF: Mibefradil, a T-type and L-type calcium channel blocker, limits infarct size through a glibenclamide-sensitive mechanism. Cardiovasc Drugs Ther. 1999 Apr;13(2):115-22. [Article]
- Jimenez C, Bourinet E, Leuranguer V, Richard S, Snutch TP, Nargeot J: Determinants of voltage-dependent inactivation affect Mibefradil block of calcium channels. Neuropharmacology. 2000;39(1):1-10. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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 ina...
- Gene Name
- CACNB3
- Uniprot ID
- P54284
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit beta-3
- Molecular Weight
- 54531.425 Da
References
- Lee TS, Kaku T, Takebayashi S, Uchino T, Miyamoto S, Hadama T, Perez-Reyes E, Ono K: Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms. Pharmacology. 2006;78(1):11-20. Epub 2006 Aug 7. [Article]
- Mocanu MM, Gadgil S, Yellon DM, Baxter GF: Mibefradil, a T-type and L-type calcium channel blocker, limits infarct size through a glibenclamide-sensitive mechanism. Cardiovasc Drugs Ther. 1999 Apr;13(2):115-22. [Article]
- Jimenez C, Bourinet E, Leuranguer V, Richard S, Snutch TP, Nargeot J: Determinants of voltage-dependent inactivation affect Mibefradil block of calcium channels. Neuropharmacology. 2000;39(1):1-10. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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 ina...
- Gene Name
- CACNB4
- Uniprot ID
- O00305
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit beta-4
- Molecular Weight
- 58168.625 Da
References
- Lee TS, Kaku T, Takebayashi S, Uchino T, Miyamoto S, Hadama T, Perez-Reyes E, Ono K: Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms. Pharmacology. 2006;78(1):11-20. Epub 2006 Aug 7. [Article]
- Mocanu MM, Gadgil S, Yellon DM, Baxter GF: Mibefradil, a T-type and L-type calcium channel blocker, limits infarct size through a glibenclamide-sensitive mechanism. Cardiovasc Drugs Ther. 1999 Apr;13(2):115-22. [Article]
- Jimenez C, Bourinet E, Leuranguer V, Richard S, Snutch TP, Nargeot J: Determinants of voltage-dependent inactivation affect Mibefradil block of calcium channels. Neuropharmacology. 2000;39(1):1-10. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid 11-beta-monooxygenase activity
- Specific Function
- Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochro...
- Gene Name
- CYP11B1
- Uniprot ID
- P15538
- Uniprot Name
- Cytochrome P450 11B1, mitochondrial
- Molecular Weight
- 57572.44 Da
References
- Imagawa K, Okayama S, Takaoka M, Kawata H, Naya N, Nakajima T, Horii M, Uemura S, Saito Y: Inhibitory effect of efonidipine on aldosterone synthesis and secretion in human adrenocarcinoma (H295R) cells. J Cardiovasc Pharmacol. 2006 Jan;47(1):133-8. doi: 10.1097/01.fjc.0000197539.12685.f5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid 11-beta-monooxygenase activity
- Specific Function
- Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone.
- Gene Name
- CYP11B2
- Uniprot ID
- P19099
- Uniprot Name
- Cytochrome P450 11B2, mitochondrial
- Molecular Weight
- 57559.62 Da
References
- Imagawa K, Okayama S, Takaoka M, Kawata H, Naya N, Nakajima T, Horii M, Uemura S, Saito Y: Inhibitory effect of efonidipine on aldosterone synthesis and secretion in human adrenocarcinoma (H295R) cells. J Cardiovasc Pharmacol. 2006 Jan;47(1):133-8. doi: 10.1097/01.fjc.0000197539.12685.f5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Backman JT, Wang JS, Wen X, Kivisto KT, Neuvonen PJ: Mibefradil but not isradipine substantially elevates the plasma concentrations of the CYP3A4 substrate triazolam. Clin Pharmacol Ther. 1999 Oct;66(4):401-7. doi: 10.1053/cp.1999.v66.a101461. [Article]
- Veronese ML, Gillen LP, Dorval EP, Hauck WW, Waldman SA, Greenberg HE: Effect of mibefradil on CYP3A4 in vivo. J Clin Pharmacol. 2003 Oct;43(10):1091-100. doi: 10.1177/0091270003256687. [Article]
- Quesada A, Bui PH, Homanics GE, Hankinson O, Handforth A: Comparison of mibefradil and derivative NNC 55-0396 effects on behavior, cytochrome P450 activity, and tremor in mouse models of essential tremor. Eur J Pharmacol. 2011 May 20;659(1):30-6. doi: 10.1016/j.ejphar.2011.01.004. Epub 2011 Jan 21. [Article]
- Bui PH, Quesada A, Handforth A, Hankinson O: The mibefradil derivative NNC55-0396, a specific T-type calcium channel antagonist, exhibits less CYP3A4 inhibition than mibefradil. Drug Metab Dispos. 2008 Jul;36(7):1291-9. doi: 10.1124/dmd.107.020115. Epub 2008 Apr 14. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Data supported by in vitro studies only.
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase 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...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Bui PH, Quesada A, Handforth A, Hankinson O: The mibefradil derivative NNC55-0396, a specific T-type calcium channel antagonist, exhibits less CYP3A4 inhibition than mibefradil. Drug Metab Dispos. 2008 Jul;36(7):1291-9. doi: 10.1124/dmd.107.020115. Epub 2008 Apr 14. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Bui PH, Quesada A, Handforth A, Hankinson O: The mibefradil derivative NNC55-0396, a specific T-type calcium channel antagonist, exhibits less CYP3A4 inhibition than mibefradil. Drug Metab Dispos. 2008 Jul;36(7):1291-9. doi: 10.1124/dmd.107.020115. Epub 2008 Apr 14. [Article]
- Wandel C, Kim RB, Guengerich FP, Wood AJ: Mibefradil is a P-glycoprotein substrate and a potent inhibitor of both P-glycoprotein and CYP3A in vitro. Drug Metab Dispos. 2000 Aug;28(8):895-8. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57525.03 Da
References
- Bui PH, Quesada A, Handforth A, Hankinson O: The mibefradil derivative NNC55-0396, a specific T-type calcium channel antagonist, exhibits less CYP3A4 inhibition than mibefradil. Drug Metab Dispos. 2008 Jul;36(7):1291-9. doi: 10.1124/dmd.107.020115. Epub 2008 Apr 14. [Article]
- Wandel C, Kim RB, Guengerich FP, Wood AJ: Mibefradil is a P-glycoprotein substrate and a potent inhibitor of both P-glycoprotein and CYP3A in vitro. Drug Metab Dispos. 2000 Aug;28(8):895-8. [Article]
- Flockhart Table of Drug Interactions [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Wandel C, Kim RB, Guengerich FP, Wood AJ: Mibefradil is a P-glycoprotein substrate and a potent inhibitor of both P-glycoprotein and CYP3A in vitro. Drug Metab Dispos. 2000 Aug;28(8):895-8. [Article]
- Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, Wikel JH, Wrighton SA: Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol Pharmacol. 2002 May;61(5):964-73. [Article]
- Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [Article]
- Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [Article]
- Bui PH, Quesada A, Handforth A, Hankinson O: The mibefradil derivative NNC55-0396, a specific T-type calcium channel antagonist, exhibits less CYP3A4 inhibition than mibefradil. Drug Metab Dispos. 2008 Jul;36(7):1291-9. doi: 10.1124/dmd.107.020115. Epub 2008 Apr 14. [Article]
- Broccatelli F, Carosati E, Neri A, Frosini M, Goracci L, Oprea TI, Cruciani G: A novel approach for predicting P-glycoprotein (ABCB1) inhibition using molecular interaction fields. J Med Chem. 2011 Mar 24;54(6):1740-51. doi: 10.1021/jm101421d. Epub 2011 Feb 22. [Article]
Drug created at July 06, 2007 20:41 / Updated at January 14, 2023 19:03