Nilvadipine
Identification
- Name
- Nilvadipine
- Accession Number
- DB06712
- Description
Nilvadipine is a calcium channel blocker (CCB) for treatment of hypertension.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Nilvadipine (DB06712)
- Weight
- Average: 385.3707
Monoisotopic: 385.127385355 - Chemical Formula
- C19H19N3O6
- Synonyms
- Nilvadipine
- Nilvadipino
- Nilvadipinum
- External IDs
- CL 287,389
- FK 235
- FR-34235
- SK&F 102,362
Pharmacology
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:Accelerate your drug discovery research with our fully connected ADMET dataset- Indication
For the management of vasospastic angina, chronic stable angina and hypertension.
- Associated Conditions
- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
Nilvadipine is similar to other dihydropyridines including amlodipine, felodipine, isradipine, and nicardipine. Nilvadipine is used to treat Prinzmetal's angina, hypertension, and other vascular disorders such as Raynaud's phenomenon. By blocking the calcium channels, Nifedipine inhibits the spasm of the coronary artery and dilates the systemic arteries, results in a increase of myocardial oxygen supply and a decrease in systemic blood pressure.
- Mechanism of action
Nilvadipine inhibits the influx of extracellular calcium through myocardial and vascular membrane pores by physically plugging the channel. The decrease in intracellular calcium inhibits the contractile processes of smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
Target Actions Organism AVoltage-dependent L-type calcium channel subunit alpha-1C inhibitorHumans AVoltage-dependent calcium channel subunit alpha-2/delta-1 inhibitorHumans AVoltage-dependent L-type calcium channel subunit beta-2 inhibitorHumans UVoltage-dependent L-type calcium channel subunit alpha-1D inhibitorHumans UVoltage-dependent L-type calcium channel subunit alpha-1S inhibitorHumans UVoltage-dependent calcium channel subunit alpha-2/delta-3 inhibitorHumans - Absorption
- Not Available
- Volume of distribution
- Not Available
- Protein binding
- Not Available
- Metabolism
- Not Available
- Route of elimination
- Not Available
- Half-life
- Not Available
- Clearance
- Not Available
- Adverse Effects
Reduce medical errorsand improve treatment outcomes with our comprehensive & structured data on drug adverse effects.Reduce medical errors & improve treatment outcomes with our adverse effects data- Toxicity
- Not Available
- Affected organisms
- Not Available
- 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 softwareAbametapir The serum concentration of Nilvadipine can be increased when it is combined with Abametapir. Abatacept The metabolism of Nilvadipine can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Nilvadipine. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Nilvadipine. Acarbose The risk or severity of hypoglycemia can be increased when Nilvadipine is combined with Acarbose. Acebutolol The risk or severity of bradycardia can be increased when Acebutolol is combined with Nilvadipine. Aceclofenac The therapeutic efficacy of Nilvadipine can be decreased when used in combination with Aceclofenac. Acemetacin The therapeutic efficacy of Nilvadipine can be decreased when used in combination with Acemetacin. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Nilvadipine. Acetaminophen Nilvadipine may increase the hepatotoxic activities of Acetaminophen. 
Improve patient outcomesBuild effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.Learn more - Food Interactions
- Take with or without food.
Products
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- International/Other Brands
- Nivadil
Categories
- ATC Codes
- C08CA10 — Nilvadipine
- 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 CYP2A6 Inhibitors
- Cytochrome P-450 CYP2A6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2E1 Substrates
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (moderate)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Dihydropyridine Derivatives
- Dihydropyridines
- Hypotensive Agents
- Membrane Transport Modulators
- Moderate Risk QTc-Prolonging Agents
- Pyridines
- QTc Prolonging Agents
- Selective Calcium Channel Blockers With Mainly Vascular Effects
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dihydropyridinecarboxylic acids and derivatives. These are compounds containing a dihydropyridine moiety bearing a carboxylic acid group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyridines and derivatives
- Sub Class
- Hydropyridines
- Direct Parent
- Dihydropyridinecarboxylic acids and derivatives
- Alternative Parents
- Nitrobenzenes / Nitroaromatic compounds / Dicarboxylic acids and derivatives / Vinylogous amides / Enoate esters / Methyl esters / Amino acids and derivatives / Propargyl-type 1,3-dipolar organic compounds / Nitriles / Azacyclic compounds show 7 more
- Substituents
- Allyl-type 1,3-dipolar organic compound / Alpha,beta-unsaturated carboxylic ester / Amine / Amino acid or derivatives / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / C-nitro compound / Carbonitrile / Carbonyl group show 25 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
Chemical Identifiers
- UNII
- 0214FUT37J
- CAS number
- 75530-68-6
- InChI Key
- FAIIFDPAEUKBEP-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H19N3O6/c1-10(2)28-19(24)15-11(3)21-14(9-20)17(18(23)27-4)16(15)12-6-5-7-13(8-12)22(25)26/h5-8,10,16,21H,1-4H3
- IUPAC Name
- 3-methyl 5-propan-2-yl 2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
- SMILES
- COC(=O)C1=C(NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC(C)C)C#N
References
- Synthesis Reference
Minoru Nakano, Toshinobu Uemura, Shinichi Morizane, Kiyoshi Okuda, Keiko Nakata, "Method of producing a solid dispersion of the sparingly water-soluble drug, nilvadipine." U.S. Patent US5340591, issued March, 1985.
US5340591- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015657
- KEGG Drug
- D01908
- PubChem Compound
- 4494
- PubChem Substance
- 99443264
- ChemSpider
- 4338
- BindingDB
- 50103634
- 53692
- ChEBI
- 31911
- ChEMBL
- CHEMBL517427
- PharmGKB
- PA165958385
- Wikipedia
- Nilvadipine
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Alzheimer's Disease (AD) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule, extended release Oral Capsule Oral Tablet, film coated Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0124 mg/mL ALOGPS logP 2.97 ALOGPS logP 2.24 ChemAxon logS -4.5 ALOGPS pKa (Strongest Basic) -0.57 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 6 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 134.24 Å2 ChemAxon Rotatable Bond Count 7 ChemAxon Refractivity 101.8 m3·mol-1 ChemAxon Polarizability 37.54 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9377 Blood Brain Barrier - 0.9749 Caco-2 permeable + 0.6864 P-glycoprotein substrate Substrate 0.5516 P-glycoprotein inhibitor I Inhibitor 0.915 P-glycoprotein inhibitor II Inhibitor 0.9125 Renal organic cation transporter Non-inhibitor 0.9071 CYP450 2C9 substrate Non-substrate 0.8306 CYP450 2D6 substrate Non-substrate 0.8932 CYP450 3A4 substrate Substrate 0.7268 CYP450 1A2 substrate Inhibitor 0.7753 CYP450 2C9 inhibitor Inhibitor 0.5318 CYP450 2D6 inhibitor Non-inhibitor 0.9291 CYP450 2C19 inhibitor Inhibitor 0.6042 CYP450 3A4 inhibitor Inhibitor 0.6375 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8599 Ames test Non AMES toxic 0.6114 Carcinogenicity Non-carcinogens 0.5194 Biodegradation Not ready biodegradable 0.995 Rat acute toxicity 2.5335 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7842 hERG inhibition (predictor II) Non-inhibitor 0.8944
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-004i-0179000000-b1d9dd06d2542abddd3c
Targets
Accelerate your drug discovery research
with our fully connected ADMET & drug target dataset.
Accelerate your drug discovery research with our ADMET & drug target dataset
- 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
- Rosenthal J: Nilvadipine: profile of a new calcium antagonist. An overview. J Cardiovasc Pharmacol. 1994;24 Suppl 2:S92-107. [PubMed:7898101]
- Morel N, Buryi V, Feron O, Gomez JP, Christen MO, Godfraind T: The action of calcium channel blockers on recombinant L-type calcium channel alpha1-subunits. Br J Pharmacol. 1998 Nov;125(5):1005-12. [PubMed:9846638]
- Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-...
- Gene Name
- CACNA2D1
- Uniprot ID
- P54289
- Uniprot Name
- Voltage-dependent calcium channel subunit alpha-2/delta-1
- Molecular Weight
- 124566.93 Da
References
- Li GR, Deng XL, Sun H, Chung SS, Tse HF, Lau CP: Ion channels in mesenchymal stem cells from rat bone marrow. Stem Cells. 2006 Jun;24(6):1519-28. Epub 2006 Feb 16. [PubMed:16484345]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Araie M, Mayama C: Use of calcium channel blockers for glaucoma. Prog Retin Eye Res. 2011 Jan;30(1):54-71. doi: 10.1016/j.preteyeres.2010.09.002. Epub 2010 Oct 8. [PubMed:20933604]
- 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
- Rosenthal J: Nilvadipine: profile of a new calcium antagonist. An overview. J Cardiovasc Pharmacol. 1994;24 Suppl 2:S92-107. [PubMed:7898101]
- Honerjager P, Seibel K: Pharmacodynamics of nilvadipine, a new dihydropyridine-type calcium antagonist. J Cardiovasc Pharmacol. 1992;20 Suppl 6:S15-21. [PubMed:1283184]
- Araie M, Mayama C: Use of calcium channel blockers for glaucoma. Prog Retin Eye Res. 2011 Jan;30(1):54-71. doi: 10.1016/j.preteyeres.2010.09.002. Epub 2010 Oct 8. [PubMed:20933604]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Sinnegger-Brauns MJ, Huber IG, Koschak A, Wild C, Obermair GJ, Einzinger U, Hoda JC, Sartori SB, Striessnig J: Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. Mol Pharmacol. 2009 Feb;75(2):407-14. doi: 10.1124/mol.108.049981. Epub 2008 Nov 24. [PubMed:19029287]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Peterson BZ, Catterall WA: Allosteric interactions required for high-affinity binding of dihydropyridine antagonists to Ca(V)1.1 Channels are modulated by calcium in the pore. Mol Pharmacol. 2006 Aug;70(2):667-75. Epub 2006 May 4. [PubMed:16675661]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Voltage-gated ion channel activity
- Specific Function
- The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-t...
- Gene Name
- CACNA2D3
- Uniprot ID
- Q8IZS8
- Uniprot Name
- Voltage-dependent calcium channel subunit alpha-2/delta-3
- Molecular Weight
- 123010.22 Da
References
- Furukawa T, Nukada T, Suzuki K, Fujita Y, Mori Y, Nishimura M, Yamanaka M: Voltage and pH dependent block of cloned N-type Ca2+ channels by amlodipine. Br J Pharmacol. 1997 Jul;121(6):1136-40. [PubMed:9249249]
- Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. [PubMed:10525060]
- Miyashita Y, Furukawa T, Kamegaya E, Yoshii M, Nukada T: A region of N-type Ca(2+) channel critical for blockade by the dihydropyridine amlodipine. Eur J Pharmacol. 2010 Apr 25;632(1-3):14-22. doi: 10.1016/j.ejphar.2010.01.006. Epub 2010 Jan 22. [PubMed:20097194]
- Murakami M, Nakagawasai O, Fujii S, Kameyama K, Murakami S, Hozumi S, Esashi A, Taniguchi R, Yanagisawa T, Tan-no K, Tadano T, Kitamura K, Kisara K: Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice. Eur J Pharmacol. 2001 May 11;419(2-3):175-81. [PubMed:11426839]
- Ogihara T, Kano T, Kakinuma C: Evaluation of the inhibitory effect of dihydropyridines on N-type calcium channel by virtual three-dimensional pharmacophore modeling. Arzneimittelforschung. 2009;59(6):283-8. doi: 10.1055/s-0031-1296398. [PubMed:19634509]
- Qu YL, Sugiyama K, Ohnuki T, Hattori K, Watanabe K, Nagatomo T: Comparison of binding affinities of omega-conotoxin and amlodipine to N-type Ca2+ channels in rat brain. Zhongguo Yao Li Xue Bao. 1998 Mar;19(2):97-100. [PubMed:10374627]
Enzymes
- 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
- Niwa T, Shiraga T, Hashimoto T, Kagayama A: Effect of nilvadipine, a dihydropyridine calcium antagonist, on cytochrome P450 activities in human hepatic microsomes. Biol Pharm Bull. 2004 Mar;27(3):415-7. [PubMed:14993813]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
- Gene Name
- CYP2A6
- Uniprot ID
- P11509
- Uniprot Name
- Cytochrome P450 2A6
- Molecular Weight
- 56501.005 Da
References
- Niwa T, Shiraga T, Hashimoto T, Kagayama A: Effect of nilvadipine, a dihydropyridine calcium antagonist, on cytochrome P450 activities in human hepatic microsomes. Biol Pharm Bull. 2004 Mar;27(3):415-7. [PubMed:14993813]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Current data supporting this enzyme inhibition is limited to one in vitro study.
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Niwa T, Shiraga T, Hashimoto T, Kagayama A: Effect of nilvadipine, a dihydropyridine calcium antagonist, on cytochrome P450 activities in human hepatic microsomes. Biol Pharm Bull. 2004 Mar;27(3):415-7. [PubMed:14993813]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid 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 oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Niwa T, Shiraga T, Hashimoto T, Kagayama A: Effect of nilvadipine, a dihydropyridine calcium antagonist, on cytochrome P450 activities in human hepatic microsomes. Biol Pharm Bull. 2004 Mar;27(3):415-7. [PubMed:14993813]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Niwa T, Shiraga T, Hashimoto T, Kagayama A: Effect of nilvadipine, a dihydropyridine calcium antagonist, on cytochrome P450 activities in human hepatic microsomes. Biol Pharm Bull. 2004 Mar;27(3):415-7. [PubMed:14993813]
Drug created on May 16, 2010 17:33 / Updated on February 21, 2021 18:52