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Identification
NameNilvadipine
Accession NumberDB06712
TypeSmall Molecule
GroupsApproved
Description

Nilvadipine is a calcium channel blocker (CCB) for treatment of hypertension.

Structure
Thumb
Synonyms
Nivadil
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
NivadilNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII0214FUT37J
CAS number75530-68-6
WeightAverage: 385.3707
Monoisotopic: 385.127385355
Chemical FormulaC19H19N3O6
InChI KeyInChIKey=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
Taxonomy
ClassificationNot classified
Pharmacology
IndicationFor the management of vasospastic angina, chronic stable angina and hypertension.
PharmacodynamicsNilvadipine 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 actionNilvadipine 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9377
Blood Brain Barrier-0.9749
Caco-2 permeable+0.6864
P-glycoprotein substrateSubstrate0.5516
P-glycoprotein inhibitor IInhibitor0.915
P-glycoprotein inhibitor IIInhibitor0.9125
Renal organic cation transporterNon-inhibitor0.9071
CYP450 2C9 substrateNon-substrate0.8306
CYP450 2D6 substrateNon-substrate0.8932
CYP450 3A4 substrateSubstrate0.7268
CYP450 1A2 substrateInhibitor0.7753
CYP450 2C9 inhibitorInhibitor0.5318
CYP450 2D6 inhibitorNon-inhibitor0.9291
CYP450 2C19 inhibitorInhibitor0.6042
CYP450 3A4 inhibitorInhibitor0.6375
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8599
Ames testNon AMES toxic0.6114
CarcinogenicityNon-carcinogens0.5194
BiodegradationNot ready biodegradable0.995
Rat acute toxicity2.5335 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7842
hERG inhibition (predictor II)Non-inhibitor0.8944
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0124 mg/mLALOGPS
logP2.97ALOGPS
logP2.24ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)-0.57ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area134.24 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity101.8 m3·mol-1ChemAxon
Polarizability37.54 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
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 ReferencesNot Available
External Links
ATC CodesC08CA10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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, 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 belon...
Gene Name:
CACNA1C
Uniprot ID:
Q13936
Molecular Weight:
248974.1 Da
References
  1. Rosenthal J: Nilvadipine: profile of a new calcium antagonist. An overview. J Cardiovasc Pharmacol. 1994;24 Suppl 2:S92-107. [PubMed:7898101 ]
  2. 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 ]
  3. Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328 ]
Kind
Protein
Organism
Human
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-contraction coupling (By similarity).
Gene Name:
CACNA2D1
Uniprot ID:
P54289
Molecular Weight:
124566.93 Da
References
  1. 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 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  3. 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
Human
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 inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Gene Name:
CACNB2
Uniprot ID:
Q08289
Molecular Weight:
73579.925 Da
References
  1. Rosenthal J: Nilvadipine: profile of a new calcium antagonist. An overview. J Cardiovasc Pharmacol. 1994;24 Suppl 2:S92-107. [PubMed:7898101 ]
  2. Honerjager P, Seibel K: Pharmacodynamics of nilvadipine, a new dihydropyridine-type calcium antagonist. J Cardiovasc Pharmacol. 1992;20 Suppl 6:S15-21. [PubMed:1283184 ]
  3. 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
Human
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, 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 belon...
Gene Name:
CACNA1D
Uniprot ID:
Q01668
Molecular Weight:
245138.75 Da
References
  1. 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
Human
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, 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 belon...
Gene Name:
CACNA1S
Uniprot ID:
Q13698
Molecular Weight:
212348.1 Da
References
  1. 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
Human
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-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) but not T-type (CACNA1G) (By similarity).
Gene Name:
CACNA2D3
Uniprot ID:
Q8IZS8
Molecular Weight:
123010.22 Da
References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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
Human
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
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 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 N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
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. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
Gene Name:
CYP2A6
Uniprot ID:
P11509
Molecular Weight:
56501.005 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
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 or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular Weight:
56848.42 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Comments
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Drug created on May 16, 2010 11:33 / Updated on April 15, 2016 16:00