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QuickView for Mibefradil (compound)
PubChem
| Name: | Mibefradil |
|---|---|
| PubChem Compound ID: | 10393179 |
| Description: | A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE. |
| Molecular formula: | C29H40Cl2FN3O3 |
| Molecular weight: | 568.55 g/mol |
DrugBank
Identification
| Name: | Mibefradil |
|---|---|
| Name (isomeric): | DB01388 |
| Drug Type: | small molecule |
| Description: | A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE. |
| Brand: | Posicor |
| Category: | Vasodilator Agents, Calcium Channel Blockers, Antihypertensive Agents |
| CAS number: | 116644-53-2 |
Pharmacology
| Indication: | For the treatment of angina and high blood pressure. |
|---|---|
| Pharmacology: |
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 it...
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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.
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| 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 a...
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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.
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| 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. |
| Protein binding: | ≥ 99%, primarily to alpha 1-acid glycoprotein. |
| Biotransformation: | 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. |
| Half Life: | 17 to 25 hours at steady state. |
| Affected organisms: | Humans and other mammals |
Interactions
| Drug interaction: |
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Targets
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of 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
| UniProt ID: | O43497 | ||||||
|---|---|---|---|---|---|---|---|
| Gene: | CACNA1G | ||||||
| Actions: | inhibitor | ||||||
| References: |
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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
| UniProt ID: | O95180 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Gene: | CACNA1H | ||||||||
| Actions: | inhibitor | ||||||||
| References: |
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Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the "high-voltage activated" (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds
| UniProt ID: | Q13936 | ||||
|---|---|---|---|---|---|
| Gene: | CACNA1C | ||||
| Actions: | inhibitor | ||||
| References: |
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Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the "high-voltage activated" (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA)
| UniProt ID: | Q01668 | |||
|---|---|---|---|---|
| Gene: | CACNA1D | |||
| Actions: | inhibitor | |||
| References: |
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Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1F gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the "high-voltage activated" (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA)
| UniProt ID: | O60840 | |||
|---|---|---|---|---|
| Gene: | CACNA1F | |||
| Actions: | inhibitor | |||
| References: |
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Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. Isoform alpha-1I gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. Gates in voltage ranges similar to, but higher than alpha 1G or alpha 1H
| UniProt ID: | Q9P0X4 | ||||
|---|---|---|---|---|---|
| Gene: | CACNA1I | ||||
| Actions: | inhibitor | ||||
| References: |
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Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the "high-voltage activated" (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle
| UniProt ID: | Q13698 | |||
|---|---|---|---|---|
| Gene: | CACNA1S | |||
| Actions: | inhibitor | |||
| References: |
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The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting
| UniProt ID: | Q02641 | |||
|---|---|---|---|---|
| Gene: | CACNB1 | |||
| Actions: | inhibitor | |||
| References: |
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The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting
| UniProt ID: | Q08289 | |||
|---|---|---|---|---|
| Gene: | CACNB2 | |||
| Actions: | inhibitor | |||
| References: |
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The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting
| UniProt ID: | P54284 | |||
|---|---|---|---|---|
| Gene: | CACNB3 | |||
| Actions: | inhibitor | |||
| References: |
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The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting
| UniProt ID: | O00305 | |||
|---|---|---|---|---|
| Gene: | CACNB4 | |||
| Actions: | inhibitor | |||
| References: |
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Enzymes
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide
| UniProt ID: | P08684 | ||
|---|---|---|---|
| Gene: | CYP3A4 | ||
| Actions: | substrate, inhibitor | ||
| References: |
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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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen
| UniProt ID: | P05177 | ||
|---|---|---|---|
| Gene: | CYP1A2 | ||
| Actions: | inhibitor | ||
| References: |
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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
| UniProt ID: | P10635 | ||
|---|---|---|---|
| Gene: | CYP2D6 | ||
| Actions: | inhibitor | ||
| References: |
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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 unrelated compounds, including steroids, fatty acids, and xenobiotics
| UniProt ID: | P20815 | ||
|---|---|---|---|
| Gene: | CYP3A5 | ||
| Actions: | inhibitor | ||
| References: |
|
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 unrelated compounds, including steroids, fatty acids, and xenobiotics
| UniProt ID: | P24462 | ||
|---|---|---|---|
| Gene: | CYP3A7 | ||
| Actions: | inhibitor | ||
| References: |
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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 cytochrome P450 XIB
| UniProt ID: | P15538 | |
|---|---|---|
| Gene: | CYP11B1 | |
| Actions: | inhibitor | |
| References: |
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Preferentially catalyzes the conversion of 11- deoxycorticosterone to aldosterone via corticosterone and 18- hydroxycorticosterone
| UniProt ID: | P19099 | |
|---|---|---|
| Gene: | CYP11B2 | |
| Actions: | inhibitor | |
| References: |
|
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 unrelated compounds, including steroids, fatty acids, and xenobiotics
| UniProt ID: | P04798 | |
|---|---|---|
| Gene: | CYP1A1 | |
| Actions: | inhibitor | |
| References: |
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Transporters
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
| UniProt ID: | P08183 | ||||
|---|---|---|---|---|---|
| Gene: | ABCB1 | ||||
| Actions: | inhibitor | ||||
| References: |
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