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Identification
NameNisoldipine
Accession NumberDB00401  (APRD00635)
TypeSmall Molecule
GroupsApproved
Description

Nisoldipine is a 1,4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, nisoldipine prevents calcium-dependent smooth muscle contraction and subsequent vasoconstriction. Nisoldipine may be used in alone or in combination with other agents in the management of hypertension.

Structure
Thumb
Synonyms
isobutyl methyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Nisoldipin
Nisoldipina
Nisoldipine
Nisoldipino
Nisoldipinum
Sular
External Identifiers
  • Bay K 5552
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Nisoldipinetablet, film coated, extended release8.5 mg/1oralPrasco Laboratories2012-02-272016-04-05Us
Nisoldipinetablet, film coated, extended release8.5 mg/1oralUnited Research Laboratories, Inc.2009-09-012016-04-23Us
Nisoldipinetablet, film coated, extended release34 mg/1oralUnited Research Laboratories, Inc.2009-09-012016-04-23Us
Nisoldipinetablet, film coated, extended release34 mg/1oralPrasco Laboratories2012-02-272016-04-05Us
Nisoldipinetablet, film coated, extended release25.5 mg/1oralUnited Research Laboratories, Inc.2009-09-012016-04-23Us
Nisoldipinetablet, film coated, extended release17 mg/1oralPrasco Laboratories2012-02-272016-04-05Us
Nisoldipinetablet, film coated, extended release17 mg/1oralUnited Research Laboratories, Inc.2009-09-012016-04-23Us
Sulartablet, film coated, extended release34 mg/1oralShionogi Inc.1995-02-022016-04-05Us
Sulartablet, film coated, extended release17 mg/1oralShionogi Inc.1995-02-022016-04-05Us
Sulartablet, film coated, extended release8.5 mg/1oralShionogi Inc.1995-02-022016-04-05Us
Sulartablet, film coated, extended release25.5 mg/1oralPhysicians Total Care, Inc.2009-02-242016-04-05Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Nisoldipinetablet, film coated, extended release8.5 mg/1oralMylan Pharmaceuticals Inc.2011-01-282016-04-23Us
Nisoldipinetablet, film coated, extended release40 mg/1oralPhysicians Total Care, Inc.2008-08-292016-04-05Us
Nisoldipinetablet, film coated, extended release40 mg/1oralMylan Pharmaceuticals Inc.2008-07-252016-04-23Us
Nisoldipinetablet, film coated, extended release30 mg/1oralMylan Pharmaceuticals Inc.2008-07-252016-04-23Us
Nisoldipinetablet, film coated, extended release20 mg/1oralMylan Pharmaceuticals Inc.2008-07-252016-04-23Us
Nisoldipinetablet, film coated, extended release34 mg/1oralMylan Pharmaceuticals Inc.2011-01-282016-04-23Us
Nisoldipinetablet, film coated, extended release25.5 mg/1oralMylan Pharmaceuticals Inc.2011-01-282016-04-23Us
Nisoldipinetablet, film coated, extended release17 mg/1oralMylan Pharmaceuticals Inc.2011-01-282016-04-23Us
Over the Counter ProductsNot Available
International Brands
NameCompany
BaymycardBayer
Baymycard RRBayer
Bo PingRui Yang Pharm
Di Yi XinTasly
Ji Ni Le ErJiankang Pharmaceutical
NinobarucinChoseido Pharmaceutical
NisomynardYoshindo
RiohardTaiyo Pharmaceutical
RuidiNanjing Sanrui Pharmaceutical Co.
SyscorBayer
Brand mixturesNot Available
SaltsNot Available
Categories
UNII4I8HAB65SZ
CAS number63675-72-9
WeightAverage: 388.4144
Monoisotopic: 388.16343651
Chemical FormulaC20H24N2O6
InChI KeyInChIKey=VKQFCGNPDRICFG-UHFFFAOYSA-N
InChI
InChI=1S/C20H24N2O6/c1-11(2)10-28-20(24)17-13(4)21-12(3)16(19(23)27-5)18(17)14-8-6-7-9-15(14)22(25)26/h6-9,11,18,21H,10H2,1-5H3
IUPAC Name
3-methyl 5-(2-methylpropyl) 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
SMILES
COC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC=C1[N+]([O-])=O)C(=O)OCC(C)C
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassHydropyridines
Direct ParentDihydropyridinecarboxylic acids and derivatives
Alternative Parents
Substituents
  • Nitrobenzene
  • Dihydropyridinecarboxylic acid derivative
  • Benzenoid
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Vinylogous amide
  • Alpha,beta-unsaturated carboxylic ester
  • Enoate ester
  • Methyl ester
  • Organic nitro compound
  • Organic nitrite
  • C-nitro compound
  • Carboxylic acid ester
  • Azacycle
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Organic oxoazanium
  • Enamine
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organic salt
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Organic zwitterion
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.
PharmacodynamicsNisoldipine, 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. Nisoldipine is similar to other peripheral vasodilators. Nisoldipine 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, Nisoldipine 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.
Related Articles
AbsorptionRelatively well absorbed into the systemic circulation with 87% of the radiolabeled drug recovered in urine and feces. The absolute bioavailability of nisoldipine is about 5%.
Volume of distributionNot Available
Protein binding99%
Metabolism

Pre-systemic metabolism in the gut wall, and this metabolism decreases from the proximal to the distal parts of the intestine. Nisoldipine is highly metabolized; 5 major urinary metabolites have been identified. The major biotransformation pathway appears to be the hydroxylation of the isobutyl ester. A hydroxylated derivative of the side chain, present in plasma at concentrations approximately equal to the parent compound, appears to be the only active metabolite and has about 10% of the activity of the parent compound. Cytochrome P450 enzymes are believed to play a major role in the metabolism of nisoldipine. The particular isoenzyme system responsible for its metabolism has not been identified, but other dihydropyridines are metabolized by cytochrome P450 IIIA4.

Route of eliminationAlthough 60-80% of an oral dose undergoes urinary excretion, only traces of unchanged nisoldipine are found in urine.
Half life7-12 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Nisoldipine Action PathwayDrug actionSMP00381
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9357
Blood Brain Barrier-0.947
Caco-2 permeable+0.6928
P-glycoprotein substrateSubstrate0.5548
P-glycoprotein inhibitor IInhibitor0.8824
P-glycoprotein inhibitor IIInhibitor0.9239
Renal organic cation transporterNon-inhibitor0.8925
CYP450 2C9 substrateNon-substrate0.7874
CYP450 2D6 substrateNon-substrate0.8929
CYP450 3A4 substrateSubstrate0.7366
CYP450 1A2 substrateInhibitor0.8782
CYP450 2C9 inhibitorInhibitor0.7826
CYP450 2D6 inhibitorNon-inhibitor0.9141
CYP450 2C19 inhibitorInhibitor0.7804
CYP450 3A4 inhibitorInhibitor0.8414
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8982
Ames testNon AMES toxic0.778
CarcinogenicityNon-carcinogens0.5782
BiodegradationNot ready biodegradable0.9335
Rat acute toxicity2.6277 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8882
hERG inhibition (predictor II)Non-inhibitor0.9175
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Mylan pharmaceuticals inc
  • Shionogi pharma inc
Packagers
Dosage forms
FormRouteStrength
Tablet, film coated, extended releaseoral17 mg/1
Tablet, film coated, extended releaseoral20 mg/1
Tablet, film coated, extended releaseoral25.5 mg/1
Tablet, film coated, extended releaseoral30 mg/1
Tablet, film coated, extended releaseoral34 mg/1
Tablet, film coated, extended releaseoral40 mg/1
Tablet, film coated, extended releaseoral8.5 mg/1
Prices
Unit descriptionCostUnit
Sular 25.5 mg 24 Hour tablet6.84USD tablet
Sular 34 mg 24 Hour tablet6.84USD tablet
Sular 17 mg 24 Hour tablet6.48USD tablet
Sular 34 mg tablet5.64USD tablet
Sular 17 mg tablet5.17USD tablet
Nisoldipine er 30 mg tablet5.07USD tablet
Nisoldipine er 40 mg tablet5.07USD tablet
Sular 10 mg tablet5.04USD tablet
Sular 8.5 mg 24 Hour tablet5.04USD tablet
Nisoldipine er 20 mg tablet4.65USD tablet
Sular 25.5 mg tablet4.35USD tablet
Sular 8.5 mg tablet4.13USD tablet
Sular 20 mg tablet3.37USD tablet
Sular 30 mg 24 Hour tablet3.23USD tablet
Sular 40 mg 24 Hour tablet3.23USD tablet
Sular 30 mg tablet3.1USD tablet
Sular 40 mg tablet2.61USD tablet
Sular 10 mg 24 Hour tablet2.36USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5422123 No1995-06-062012-06-06Us
US5626874 No1994-11-302014-11-30Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP3.26MASUMOTO,K ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.00577 mg/mLALOGPS
logP3.63ALOGPS
logP3.06ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)5.32ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area110.45 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity105.91 m3·mol-1ChemAxon
Polarizability39.72 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

Massimo Ferrari, Marcello Ghezzi, Manuel Alberelli, Alberto Ambrosini, “Industrial process for the synthesis of isobutyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine dicarboxylate (nisoldipine).” U.S. Patent US20050240022, issued October 27, 2005.

US20050240022
General References
  1. Mielcarek J, Grobelny P, Szamburska O: The effect of beta-carotene on the photostability of nisoldipine. Methods Find Exp Clin Pharmacol. 2005 Apr;27(3):167-71. [PubMed:15834448 ]
  2. Missan S, Zhabyeyev P, Dyachok O, Jones SE, McDonald TF: Block of cardiac delayed-rectifier and inward-rectifier K+ currents by nisoldipine. Br J Pharmacol. 2003 Nov;140(5):863-70. Epub 2003 Oct 6. [PubMed:14530219 ]
  3. Hamilton SF, Houle LM, Thadani U: Rapid-release and coat-core formulations of nisoldipine in treatment of hypertension, angina, and heart failure. Heart Dis. 1999 Nov-Dec;1(5):279-88. [PubMed:11720635 ]
External Links
ATC CodesC08CA07
AHFS Codes
  • 24:28.08
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetaminophenThe metabolism of Nisoldipine can be increased when combined with Acetaminophen.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Nisoldipine.
AlfuzosinAlfuzosin may increase the hypotensive activities of Nisoldipine.
AmifostineNisoldipine may increase the hypotensive activities of Amifostine.
AmobarbitalThe metabolism of Nisoldipine can be increased when combined with Amobarbital.
AprepitantThe serum concentration of Nisoldipine can be increased when it is combined with Aprepitant.
AtazanavirThe serum concentration of Nisoldipine can be increased when it is combined with Atazanavir.
AtosibanThe risk or severity of adverse effects can be increased when Nisoldipine is combined with Atosiban.
Atracurium besylateNisoldipine may increase the neuromuscular blocking activities of Atracurium besylate.
BepridilNisoldipine may increase the hypotensive activities of Bepridil.
BexaroteneThe serum concentration of Nisoldipine can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Nisoldipine can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Nisoldipine can be decreased when it is combined with Bosentan.
BrimonidineBrimonidine may increase the antihypertensive activities of Nisoldipine.
ButabarbitalThe metabolism of Nisoldipine can be increased when combined with Butabarbital.
ButalbitalThe metabolism of Nisoldipine can be increased when combined with Butalbital.
ButethalThe metabolism of Nisoldipine can be increased when combined with Butethal.
CaffeineThe metabolism of Nisoldipine can be increased when combined with Caffeine.
Calcium AcetateThe therapeutic efficacy of Nisoldipine can be decreased when used in combination with Calcium Acetate.
Calcium carbonateThe therapeutic efficacy of Nisoldipine can be decreased when used in combination with Calcium carbonate.
Calcium ChlorideThe therapeutic efficacy of Nisoldipine can be decreased when used in combination with Calcium Chloride.
Calcium citrateThe therapeutic efficacy of Nisoldipine can be decreased when used in combination with Calcium citrate.
Calcium gluconateThe therapeutic efficacy of Nisoldipine can be decreased when used in combination with Calcium gluconate.
CarbamazepineThe serum concentration of Nisoldipine can be decreased when it is combined with Carbamazepine.
CeritinibThe serum concentration of Nisoldipine can be increased when it is combined with Ceritinib.
CimetidineThe serum concentration of Nisoldipine can be increased when it is combined with Cimetidine.
Cisatracurium besylateNisoldipine may increase the neuromuscular blocking activities of Cisatracurium besylate.
ClarithromycinThe serum concentration of Nisoldipine can be increased when it is combined with Clarithromycin.
ClopidogrelThe therapeutic efficacy of Clopidogrel can be decreased when used in combination with Nisoldipine.
CobicistatThe serum concentration of Nisoldipine can be increased when it is combined with Cobicistat.
ConivaptanThe serum concentration of Nisoldipine can be increased when it is combined with Conivaptan.
CyclosporineThe metabolism of Nisoldipine can be decreased when combined with Cyclosporine.
DabrafenibThe serum concentration of Nisoldipine can be decreased when it is combined with Dabrafenib.
DapoxetineDapoxetine may increase the orthostatic hypotensive activities of Nisoldipine.
DarunavirThe serum concentration of Nisoldipine can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Nisoldipine can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Nisoldipine can be decreased when it is combined with Deferasirox.
DexamethasoneThe serum concentration of Nisoldipine can be decreased when it is combined with Dexamethasone.
DiazoxideDiazoxide may increase the hypotensive activities of Nisoldipine.
DoxazosinDoxazosin may increase the hypotensive activities of Nisoldipine.
DuloxetineNisoldipine may increase the orthostatic hypotensive activities of Duloxetine.
EfavirenzThe serum concentration of Nisoldipine can be decreased when it is combined with Efavirenz.
EnzalutamideThe serum concentration of Nisoldipine can be decreased when it is combined with Enzalutamide.
ErythromycinThe metabolism of Nisoldipine can be decreased when combined with Erythromycin.
Eslicarbazepine acetateThe serum concentration of Nisoldipine can be decreased when it is combined with Eslicarbazepine acetate.
EtravirineThe serum concentration of Nisoldipine can be decreased when it is combined with Etravirine.
FluconazoleThe serum concentration of Nisoldipine can be increased when it is combined with Fluconazole.
FosaprepitantThe serum concentration of Nisoldipine can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Nisoldipine can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Nisoldipine can be increased when it is combined with Fusidic Acid.
HeptabarbitalThe metabolism of Nisoldipine can be increased when combined with Heptabarbital.
HexobarbitalThe metabolism of Nisoldipine can be increased when combined with Hexobarbital.
IdelalisibThe serum concentration of Nisoldipine can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Nisoldipine can be increased when it is combined with Indinavir.
ItraconazoleThe serum concentration of Nisoldipine can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Nisoldipine can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Nisoldipine can be increased when it is combined with Ketoconazole.
LevodopaNisoldipine may increase the orthostatic hypotensive activities of Levodopa.
LuliconazoleThe serum concentration of Nisoldipine can be increased when it is combined with Luliconazole.
Magnesium chlorideThe risk or severity of adverse effects can be increased when Nisoldipine is combined with Magnesium chloride.
Magnesium citrateThe risk or severity of adverse effects can be increased when Nisoldipine is combined with Magnesium citrate.
Magnesium hydroxideThe risk or severity of adverse effects can be increased when Nisoldipine is combined with Magnesium hydroxide.
Magnesium oxideThe risk or severity of adverse effects can be increased when Nisoldipine is combined with Magnesium oxide.
Magnesium salicylateThe risk or severity of adverse effects can be increased when Nisoldipine is combined with Magnesium salicylate.
Magnesium SulfateThe risk or severity of adverse effects can be increased when Nisoldipine is combined with Magnesium Sulfate.
MelatoninMelatonin may decrease the antihypertensive activities of Nisoldipine.
MethohexitalThe metabolism of Nisoldipine can be increased when combined with Methohexital.
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Nisoldipine.
MifepristoneThe serum concentration of Nisoldipine can be increased when it is combined with Mifepristone.
MitotaneThe serum concentration of Nisoldipine can be decreased when it is combined with Mitotane.
ModafinilThe serum concentration of Nisoldipine can be decreased when it is combined with Modafinil.
MolsidomineMolsidomine may increase the hypotensive activities of Nisoldipine.
MoxonidineMoxonidine may increase the hypotensive activities of Nisoldipine.
NafcillinThe serum concentration of Nisoldipine can be decreased when it is combined with Nafcillin.
NefazodoneThe serum concentration of Nisoldipine can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Nisoldipine can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Nisoldipine can be increased when it is combined with Netupitant.
NicorandilNicorandil may increase the hypotensive activities of Nisoldipine.
NitroprussideNisoldipine may increase the hypotensive activities of Nitroprusside.
ObinutuzumabNisoldipine may increase the hypotensive activities of Obinutuzumab.
PalbociclibThe serum concentration of Nisoldipine can be increased when it is combined with Palbociclib.
PancuroniumNisoldipine may increase the neuromuscular blocking activities of Pancuronium.
PentobarbitalThe metabolism of Nisoldipine can be increased when combined with Pentobarbital.
PentoxifyllinePentoxifylline may increase the hypotensive activities of Nisoldipine.
PhenelzinePhenelzine may increase the hypotensive activities of Nisoldipine.
PhenobarbitalThe serum concentration of Nisoldipine can be decreased when it is combined with Phenobarbital.
PhenoxybenzaminePhenoxybenzamine may increase the hypotensive activities of Nisoldipine.
PhentolaminePhentolamine may increase the hypotensive activities of Nisoldipine.
PhenytoinThe serum concentration of Nisoldipine can be decreased when it is combined with Phenytoin.
PosaconazoleThe serum concentration of Nisoldipine can be increased when it is combined with Posaconazole.
PrazosinPrazosin may increase the hypotensive activities of Nisoldipine.
PrimidoneThe serum concentration of Nisoldipine can be decreased when it is combined with Primidone.
QuinineQuinine may increase the hypotensive activities of Nisoldipine.
RifabutinThe serum concentration of Nisoldipine can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Nisoldipine can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Nisoldipine can be decreased when it is combined with Rifapentine.
RisperidoneNisoldipine may increase the hypotensive activities of Risperidone.
RitonavirThe serum concentration of Nisoldipine can be increased when it is combined with Ritonavir.
RituximabNisoldipine may increase the hypotensive activities of Rituximab.
RocuroniumNisoldipine may increase the neuromuscular blocking activities of Rocuronium.
SaquinavirThe serum concentration of Nisoldipine can be increased when it is combined with Saquinavir.
SecobarbitalThe metabolism of Nisoldipine can be increased when combined with Secobarbital.
SilodosinSilodosin may increase the hypotensive activities of Nisoldipine.
SiltuximabThe serum concentration of Nisoldipine can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Nisoldipine can be increased when it is combined with Simeprevir.
StiripentolThe serum concentration of Nisoldipine can be increased when it is combined with Stiripentol.
SulfisoxazoleThe metabolism of Nisoldipine can be decreased when combined with Sulfisoxazole.
TacrolimusThe serum concentration of Tacrolimus can be increased when it is combined with Nisoldipine.
TadalafilTadalafil may increase the antihypertensive activities of Nisoldipine.
TamsulosinTamsulosin may increase the hypotensive activities of Nisoldipine.
TelaprevirThe serum concentration of Nisoldipine can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Nisoldipine can be increased when it is combined with Telithromycin.
TerazosinTerazosin may increase the hypotensive activities of Nisoldipine.
TizanidineThe serum concentration of Tizanidine can be increased when it is combined with Nisoldipine.
TocilizumabThe serum concentration of Nisoldipine can be decreased when it is combined with Tocilizumab.
TranylcypromineTranylcypromine may increase the hypotensive activities of Nisoldipine.
TreprostinilTreprostinil may increase the hypotensive activities of Nisoldipine.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Nisoldipine.
VardenafilVardenafil may increase the antihypertensive activities of Nisoldipine.
VecuroniumNisoldipine may increase the neuromuscular blocking activities of Vecuronium.
VoriconazoleThe serum concentration of Nisoldipine can be increased when it is combined with Voriconazole.
YohimbineYohimbine may decrease the antihypertensive activities of Nisoldipine.
Food Interactions
  • Do not take with grapefruit juice as this has been shown to interfere with nisoldipine metabolism, resulting in a mean increase in Cmax of about 3-fold (up to about 7-fold) and AUC of almost 2-fold (up to 5-fold).

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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Hu H, Marban E: Isoform-specific inhibition of L-type calcium channels by dihydropyridines is independent of isoform-specific gating properties. Mol Pharmacol. 1998 May;53(5):902-7. [PubMed:9584217 ]
  3. 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 ]
  4. Wei X, Pan S, Lang W, Kim H, Schneider T, Perez-Reyes E, Birnbaumer L: Molecular determinants of cardiac Ca2+ channel pharmacology. Subunit requirement for the high affinity and allosteric regulation of dihydropyridine binding. J Biol Chem. 1995 Nov 10;270(45):27106-11. [PubMed:7592963 ]
  5. 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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. 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 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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. 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 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
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-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 ]

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 ]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
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.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
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.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular Weight:
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
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 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
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
  1. 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:12128170 ]
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Drug created on June 13, 2005 07:24 / Updated on April 15, 2016 15:55