Verapamil
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Basic Info
| Common Name | Verapamil(F04853) |
| 2D Structure | |
| Description | Verapamil is only found in individuals that have used or taken this drug. Verapamil is a calcium channel blocker that is a class IV anti-arrhythmia agent. [PubChem]Verapamil inhibits voltage-dependent calcium channels. Specifically, its effect on L-type calcium channels in the heart causes a reduction in ionotropy and chronotropy, thuis reducing heart rate and blood pressure. Verapamil's mechanism of effect in cluster headache is thought to be linked to its calcium-channel blocker effect, but which channel subtypes are involved is presently not known. [PubChem] Calcium channel antagonists can be quite toxic. In the management of poisoning, early recognition is critical. Calcium channel antagonists are frequently prescribed, and the potential for serious morbidity and mortality with over dosage is significant. Ingestion of these agents should be suspected in any patient who presents in an overdose situation with unexplained hypotension and conduction abnormalities. The potential for toxicity should be noted in patients with underlying hepatic or renal dysfunction who are receiving therapeutic doses. (A7844). |
| FRCD ID | F04853 |
| CAS Number | 52-53-9 |
| PubChem CID | 2520 |
| Formula | C27H38N2O4 |
| IUPAC Name | 2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]-2-propan-2-ylpentanenitrile |
| InChI Key | SGTNSNPWRIOYBX-UHFFFAOYSA-N |
| InChI | InChI=1S/C27H38N2O4/c1-20(2)27(19-28,22-10-12-24(31-5)26(18-22)33-7)14-8-15-29(3)16-13-21-9-11-23(30-4)25(17-21)32-6/h9-12,17-18,20H,8,13-16H2,1-7H3 |
| Canonical SMILES | CC(C)C(CCCN(C)CCC1=CC(=C(C=C1)OC)OC)(C#N)C2=CC(=C(C=C2)OC)OC |
| Isomeric SMILES | CC(C)C(CCCN(C)CCC1=CC(=C(C=C1)OC)OC)(C#N)C2=CC(=C(C=C2)OC)OC |
| Wikipedia | Verapamil |
| Synonyms |
VERAPAMIL
Iproveratril
Vasolan
52-53-9
Dilacoran
Isoptin
Cordilox
Calan
Verapamilo
Verapamilum
|
| Classifies |
Predicted: Pesticide
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Benzene and substituted derivatives |
| Subclass | Phenylbutylamines |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Phenylbutylamines |
| Alternative Parents | |
| Molecular Framework | Aromatic homomonocyclic compounds |
| Substituents | Phenylbutylamine - Dimethoxybenzene - O-dimethoxybenzene - Phenethylamine - Phenylpropane - Anisole - Phenol ether - Phenoxy compound - Methoxybenzene - Alkyl aryl ether - Aralkylamine - Tertiary aliphatic amine - Tertiary amine - Nitrile - Carbonitrile - Ether - Organic oxygen compound - Amine - Organic nitrogen compound - Organooxygen compound - Organonitrogen compound - Organopnictogen compound - Hydrocarbon derivative - Aromatic homomonocyclic compound |
| Description | This compound belongs to the class of organic compounds known as phenylbutylamines. These are compounds containing a phenylbutylamine moiety, which consists of a phenyl group substituted at the fourth carbon by an butan-1-amine. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 454.611 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 13 |
| Complexity | 606 |
| Monoisotopic Mass | 454.283 |
| Exact Mass | 454.283 |
| XLogP | 3.8 |
| Formal Charge | 0 |
| Heavy Atom Count | 33 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 1 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Ca2+ influxes and transmembrane transport are essential for phytic aciddegradation in mung bean sprouts. | J Sci Food Agric | 2018 Mar | 28926677 |
| Lipid emulsion alleviates the vasodilation and mean blood pressure decrease induced by a toxic dose of verapamil in isolated rat aortae and an in vivo rat model. | Hum Exp Toxicol | 2018 Jun | 28741374 |
| Lipid Emulsion Inhibits Apoptosis Induced by a Toxic Dose of Verapamil via the Delta-Opioid Receptor in H9c2 Rat Cardiomyoblasts. | Cardiovasc Toxicol | 2017 Jul | 27990618 |
| Determination of S-methyl-L-methionine (SMM) from Brassicaceae Family Vegetables and Characterization of the Intestinal Transport of SMM by Caco-2 Cells. | J Food Sci | 2017 Jan | 27883364 |
| A quantitative determination of fluorochloridone in rat plasma by UPLC-MS/MSmethod: application to a pharmacokinetic study. | Biomed Chromatogr | 2016 Aug | 26663256 |
| Effect of biotin and pantothenic acid on performance and concentrations ofavidin-binding substances in blood and milk of lactating dairy cows. | J Dairy Sci | 2015 Sep | 26117345 |
| In vitro detection of cardiotoxins or neurotoxins affecting ion channels or pumps using beating cardiomyocytes as alternative for animal testing. | Toxicol In Vitro | 2015 Mar | 25479353 |
| Toxicity evaluation of new agricultural fungicides in primary cultured corticalneurons. | Environ Res | 2015 Jul | 25825129 |
| Demethoxycurcumin modulates human P-glycoprotein function via uncompetitiveinhibition of ATPase hydrolysis activity. | J Agric Food Chem | 2015 Jan 28 | 25594233 |
| Effect of urea inclusion in diets containing corn dried distillers grains onfeedlot cattle performance, carcass characteristics, ruminal fermentation, total tract digestibility, and purine derivatives-to-creatinine index. | J Anim Sci | 2015 Jan | 25412747 |
| Pharmacological basis for the medicinal use of Linum usitatissimum (Flaxseed) in infectious and non-infectious diarrhea. | J Ethnopharmacol | 2015 Feb 3 | 25433250 |
| Short communication: Production response of lactating dairy cows to brachyticforage sorghum silage compared with corn silage from first or second harvest. | J Dairy Sci | 2015 Dec | 26454290 |
| Mechanisms underlying turgor regulation in the estuarine alga Vaucheriaerythrospora (Xanthophyceae) exposed to hyperosmotic shock. | Plant Cell Environ | 2015 Aug | 25546818 |
| E. coli infection modulates the pharmacokinetics of oral enrofloxacin bytargeting P-glycoprotein in small intestine and CYP450 3A in liver and kidney of broilers. | PLoS One | 2014 Jan 31 | 24498193 |
| Ca(2+) efflux is involved in cinnamaldehyde-induced growth inhibition ofPhytophthora capsici. | PLoS One | 2013 Oct 1 | 24098458 |
| Effect of sulfur content in wet or dry distillers grains fed at severalinclusions on cattle growth performance, ruminal parameters, and hydrogensulfide. | J Anim Sci | 2013 Oct | 23893985 |
| Functional evidence for physiological mechanisms to circumvent neurotoxicity of cardenolides in an adapted and a non-adapted hawk-moth species. | Proc Biol Sci | 2013 May 22 | 23516239 |
| Areca nut-induced buccal mucosa fibroblast contraction and its signaling: apotential role in oral submucous fibrosis--a precancer condition. | Carcinogenesis | 2013 May | 23349021 |
| Gastro-intestinal transport of calcium and cadmium in fresh water and seawateracclimated trout (Oncorhynchus mykiss). | Comp Biochem Physiol C Toxicol Pharmacol | 2013 Mar | 23201586 |
| Transcellular transport of aconitine across human intestinal Caco-2 cells. | Food Chem Toxicol | 2013 Jul | 23562926 |
Targets
- General Function:
- Xenobiotic-transporting atpase activity
- Specific Function:
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name:
- ABCB1
- Uniprot ID:
- P08183
- Molecular Weight:
- 141477.255 Da
References
- Chang JH, Kochansky CJ, Shou M: The role of P-glycoprotein in the bioactivation of raloxifene. Drug Metab Dispos. 2006 Dec;34(12):2073-8. Epub 2006 Sep 7. [16959878 ]
- General Function:
- Serotonin:sodium symporter activity
- Specific Function:
- Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
- Gene Name:
- SLC6A4
- Uniprot ID:
- P31645
- Molecular Weight:
- 70324.165 Da
References
- Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [9537821 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function.
- Gene Name:
- CACNA1C
- Uniprot ID:
- Q13936
- Molecular Weight:
- 248974.1 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Dilmac N, Hilliard N, Hockerman GH: Molecular determinants of frequency dependence and Ca2+ potentiation of verapamil block in the pore region of Cav1.2. Mol Pharmacol. 2004 Nov;66(5):1236-47. Epub 2004 Jul 30. [15286207 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1F gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA).
- Gene Name:
- CACNA1F
- Uniprot ID:
- O60840
- Molecular Weight:
- 220675.9 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
- Gene Name:
- CACNB1
- Uniprot ID:
- Q02641
- Molecular Weight:
- 65712.995 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
- Gene Name:
- CACNB2
- Uniprot ID:
- Q08289
- Molecular Weight:
- 73579.925 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
- Gene Name:
- CACNB3
- Uniprot ID:
- P54284
- Molecular Weight:
- 54531.425 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
- Gene Name:
- CACNB4
- Uniprot ID:
- O00305
- Molecular Weight:
- 58168.625 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Voltage-gated calcium channel activity involved sa node cell action potential
- Specific Function:
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA).
- Gene Name:
- CACNA1D
- Uniprot ID:
- Q01668
- Molecular Weight:
- 245138.75 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Morgan EL, Mace OJ, Affleck J, Kellett GL: Apical GLUT2 and Cav1.3: regulation of rat intestinal glucose and calcium absorption. J Physiol. 2007 Apr 15;580(Pt. 2):593-604. Epub 2007 Feb 1. [17272350 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only as a multiple subunit complex.
- Gene Name:
- CACNG1
- Uniprot ID:
- Q06432
- Molecular Weight:
- 25028.105 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Protein heterodimerization activity
- Specific Function:
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
- Gene Name:
- ADRA1B
- Uniprot ID:
- P35368
- Molecular Weight:
- 56835.375 Da
References
- Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [9570190 ]
- General Function:
- Alpha1-adrenergic receptor activity
- Specific Function:
- This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
- Gene Name:
- ADRA1D
- Uniprot ID:
- P25100
- Molecular Weight:
- 60462.205 Da
References
- Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [9570190 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
- Gene Name:
- CA1
- Uniprot ID:
- P00915
- Molecular Weight:
- 28870.0 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.
- Gene Name:
- CACNA1B
- Uniprot ID:
- Q00975
- Molecular Weight:
- 262493.84 Da
References
- Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. doi: 10.1111/j.1526-4610.2008.01298.x. [19125880 ]
- General Function:
- Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
- Specific Function:
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
- Gene Name:
- KCNH2
- Uniprot ID:
- Q12809
- Molecular Weight:
- 126653.52 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Duan JJ, Ma JH, Zhang PH, Wang XP, Zou AR, Tu DN: Verapamil blocks HERG channel by the helix residue Y652 and F656 in the S6 transmembrane domain. Acta Pharmacol Sin. 2007 Jul;28(7):959-67. [17588331 ]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium (By similarity). Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation.
- Gene Name:
- KCNJ11
- Uniprot ID:
- Q14654
- Molecular Weight:
- 43540.375 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle.
- Gene Name:
- CACNA1S
- Uniprot ID:
- Q13698
- Molecular Weight:
- 212348.1 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Scaffold protein binding
- Specific Function:
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channel is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.
- Gene Name:
- CACNA1G
- Uniprot ID:
- O43497
- Molecular Weight:
- 262468.62 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. Isoform alpha-1I gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. Gates in voltage ranges similar to, but higher than alpha 1G or alpha 1H (By similarity).
- Gene Name:
- CACNA1I
- Uniprot ID:
- Q9P0X4
- Molecular Weight:
- 245100.8 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Voltage-gated sodium channel activity involved in sa node cell action potential
- Specific Function:
- This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
- Gene Name:
- SCN5A
- Uniprot ID:
- Q14524
- Molecular Weight:
- 226937.475 Da
- Mechanism of Action:
- Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
References
- Milberg P, Reinsch N, Osada N, Wasmer K, Monnig G, Stypmann J, Breithardt G, Haverkamp W, Eckardt L: Verapamil prevents torsade de pointes by reduction of transmural dispersion of repolarization and suppression of early afterdepolarizations in an intact heart model of LQT3. Basic Res Cardiol. 2005 Jul;100(4):365-71. Epub 2005 Jun 10. [15944809 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by the funnel toxin (Ftx) and by the omega-agatoxin-IVA (omega-Aga-IVA). They are however insensitive to dihydropyridines (DHP), and omega-conotoxin-GVIA (omega-CTx-GVIA).
- Gene Name:
- CACNA1A
- Uniprot ID:
- O00555
- Molecular Weight:
- 282362.39 Da
References
- Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. doi: 10.1111/j.1526-4610.2008.01298.x. [19125880 ]