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Identification
NameNitrendipine
Accession NumberDB01054  (APRD00421)
Typesmall molecule
Groupsapproved
Description

A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
NitrendipinoSpanishINN
NitrendipinumLatinINN
SaltsNot Available
Brand names
NameCompany
BayotensinNot Available
BaypressNot Available
DeitenNot Available
NidrelNot Available
NitrepinNot Available
NitrezicNot Available
Brand mixturesNot Available
Categories
CAS number39562-70-4
WeightAverage: 360.3612
Monoisotopic: 360.132136382
Chemical FormulaC18H20N2O6
InChI KeyInChIKey=PVHUJELLJLJGLN-UHFFFAOYSA-N
InChI
InChI=1S/C18H20N2O6/c1-5-26-18(22)15-11(3)19-10(2)14(17(21)25-4)16(15)12-7-6-8-13(9-12)20(23)24/h6-9,16,19H,5H2,1-4H3
IUPAC Name
3-ethyl 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
SMILES
CCOC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPyridines and Derivatives
SubclassHydropyridines
Direct parentDihydropyridinecarboxylic Acids and Derivatives
Alternative parentsNitrobenzenes; Dicarboxylic Acids and Derivatives; Nitronic Acids; Carboxylic Acid Esters; Nitro Compounds; Ethers; Enolates; Enamines; Organic Oxoazanium Compounds; Polyamines
Substituentsbenzene; dicarboxylic acid derivative; carboxylic acid ester; nitro compound; nitronic acid; polyamine; carboxylic acid derivative; organic oxoazanium; ether; enolate; enamine; organonitrogen compound; amine
Classification descriptionThis compound belongs to the dihydropyridinecarboxylic acids and derivatives. These are compounds containing a dihydropyridine moiety bearing a carboxylic acid group.
Pharmacology
IndicationFor the treatment of mild to moderate hypertension
PharmacodynamicsNitrendipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nitrendipine is similar to other peripheral vasodilators. Nitrendipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial 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.
Mechanism of actionBy deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, Nitrendipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding> 99%
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Nitrendipine Action PathwayDrug actionSMP00382
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9536
Blood Brain Barrier - 0.9549
Caco-2 permeable + 0.7853
P-glycoprotein substrate Substrate 0.5265
P-glycoprotein inhibitor I Inhibitor 0.8564
P-glycoprotein inhibitor II Inhibitor 0.8313
Renal organic cation transporter Non-inhibitor 0.8984
CYP450 2C9 substrate Non-substrate 0.8212
CYP450 2D6 substrate Non-substrate 0.8931
CYP450 3A4 substrate Substrate 0.7266
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Inhibitor 0.8949
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Inhibitor 0.8993
CYP450 3A4 substrate Inhibitor 0.8037
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9247
Ames test Non AMES toxic 0.7334
Carcinogenicity Non-carcinogens 0.5186
Biodegradation Not ready biodegradable 0.9581
Rat acute toxicity 2.3810 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8131
hERG inhibition (predictor II) Non-inhibitor 0.9094
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point156-160 °CNot Available
water solubilityInsolubleNot Available
logP2.88MASUMATO,K ET AL. (1995)
Caco2 permeability-4.77ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility1.42e-02 g/lALOGPS
logP3.21ALOGPS
logP2.17ChemAxon
logS-4.4ALOGPS
pKa (strongest basic)5.43ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count1ChemAxon
polar surface area110.45ChemAxon
rotatable bond count7ChemAxon
refractivity96.91ChemAxon
polarizability36.25ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Wolfgang Schmidt, Bernhard Streuff, Manfred Winter, “Preparation of solid medicament formulation containing nitrendipine.” U.S. Patent US4724141, issued April, 1980.

US4724141
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00629
KEGG CompoundC07713
PubChem Compound4507
PubChem Substance46508817
ChemSpider4351
BindingDB50012016
Therapeutic Targets DatabaseDAP001263
PharmGKBPA146096020
IUPHAR2334
Guide to Pharmacology2334
WikipediaNitrendipine
ATC CodesC08CA08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
CimetidineCimetidine increases the effect of the calcium channel blocker, nitrendipine.
TelithromycinTelithromycin may reduce clearance of Nitrendipine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Nitrendipine if Telithromycin is initiated, discontinued or dose changed.
ThiopentalThe CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Nitrendipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Nitrendipine if Thiopental is initiated, discontinued or dose changed.
TipranavirTipranavir may decrease the metabolism and clearance of the calcium channel blocker, Nitrendipine. Monitor for changes in Nitrendipine therapeutic and adverse effects if Tipranavir is initiated, discontinued or dose changed.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of nitrendipine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nitrendipine if voriconazole is initiated, discontinued or dose changed.
Food InteractionsNot Available

1. Voltage-dependent L-type calcium channel subunit alpha-1C

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent L-type calcium channel subunit alpha-1C Q13936 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Striessnig, J. (2004). Ca 2+ channel blockers. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin, Germany: Springer.

2. Voltage-dependent calcium channel subunit alpha-2/delta-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent calcium channel subunit alpha-2/delta-1 P54289 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Striessnig, J. (2004). Ca 2+ channel blockers. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin, Germany: Springer.

3. Voltage-dependent L-type calcium channel subunit beta-2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent L-type calcium channel subunit beta-2 Q08289 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Striessnig, J. (2004). Ca 2+ channel blockers. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin, Germany: Springer.

4. Voltage-dependent calcium channel gamma-1 subunit

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent calcium channel gamma-1 subunit Q06432 Details

References:

  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed

5. Voltage-dependent L-type calcium channel subunit alpha-1D

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent L-type calcium channel subunit alpha-1D Q01668 Details

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. Epub 2008 Nov 24. Pubmed

6. Voltage-dependent L-type calcium channel subunit alpha-1S

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent L-type calcium channel subunit alpha-1S Q13698 Details

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

7. Voltage-dependent calcium channel subunit alpha-2/delta-2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent calcium channel subunit alpha-2/delta-2 Q9NY47 Details

References:

  1. Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. Epub 2008 Oct 30. Pubmed

8. Voltage-dependent T-type calcium channel subunit alpha-1H

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent T-type calcium channel subunit alpha-1H O95180 Details

References:

  1. Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. Epub 2008 Oct 30. Pubmed

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. Pubmed
  2. Takara K, Sakaeda T, Tanigawara Y, Nishiguchi K, Ohmoto N, Horinouchi M, Komada F, Ohnishi N, Yokoyama T, Okumura K: Effects of 12 Ca2+ antagonists on multidrug resistance, MDR1-mediated transport and MDR1 mRNA expression. Eur J Pharm Sci. 2002 Aug;16(3):159-65. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on March 11, 2014 08:41