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Details

Stereochemistry RACEMIC
Molecular Formula C20H24N2O6
Molecular Weight 388.4151
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NISOLDIPINE

SMILES

CC(C)COC(=O)C1=C(C)NC(=C(C1c2ccccc2N(=O)=O)C(=O)OC)C

InChI

InChIKey=VKQFCGNPDRICFG-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C20H24N2O6
Molecular Weight 388.4151
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment:: Description was created based on several sources, including: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcdeafac-f4ef-4dda-bdb7-1f819c33bb76 Pharmaceutical Innovation: Revolutionizing Human Health/ Editors. R. Landau, B. Achilladelis, A. Scriabine Chemical Heritage Foundation, 1999 -P. 408 ISBN 0-941901-21-1

Nisoldipine is a 1,4-dihydropyridine derivative with an outstanding vascular selectivity. As a specific calcium antagonist, it shortens the action potential and causes electromechanical uncoupling in ventricular myocardium. However, this effect, resulting in a negative inotropic action, appears at 100–1000 times higher concentrations of nisoldipine in comparison with its inhibition of calcium-dependent vascular contractions. Detailed analyses of pharmacological effects revealed additional properties such as enhancement of sodium excretion, an interaction with the reninangiotensin-aldosterone system and a protective effect against acute renal ischaemia, that may contribute to its therapeutic efficacy. Nisoldipine was developed at Bayer then licensed to Zeneca and marketed in the United States as SULAR. SULAR is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents. The mechanism of the therapeutic effect of nisoldipine is complex. It involves a decrease of the total peripheral vascular resistance (reduction of afterload) and an increase in coronary blood flow. Moreover, nisoldipine obviously normalises the impaired volume homoeostasis by improving renal function and thus reduces the need for activation of the ANP system. In the advanced stages of hypertension, nisoldipine prevents deleterious calcium overload and the resulting tissue damage.

CNS Activity

Curator's Comment:: Nisoldipine was active in rat brain toward monoamines and metabolites. In human nisoldipine does not have any cognition enhancing properties but, unlike some calcium antagonists, it does not markedly impair CNS activity. https://www.ncbi.nlm.nih.gov/pubmed/12404341

Originator

Sources: Pharmaceutical Innovation: Revolutionizing Human Health/ Ed. R. Landau, B. Achilladelis, A. Scriabine Chemical Heritage Foundation, 1999 -P. 408 ISBN 0-941901-21-1
Curator's Comment:: # Bayer

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.04 nM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
SULAR

Approved Use

Nisoldipine extended-release tablets are indicated for the treatment of hypertension. They may be used alone or in combination with other antihypertensive agents.

Launch Date

7.916832E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.44 ng/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NISOLDIPINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.26 ng/mL
20 mg 1 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
NISOLDIPINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3.4 ng/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NISOLDIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
19.06 ng × h/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NISOLDIPINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
29.42 ng × h/mL
20 mg 1 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
NISOLDIPINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
54 mg × h/mL/(mg dose/kg)
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NISOLDIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12.61 h
20 mg 1 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
NISOLDIPINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
9.7 h
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NISOLDIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.27%
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NISOLDIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Co-administed with::
atenolol(50 mg four times daily)
Sources:
unhealthy, adult
n = 503
Health Status: unhealthy
Condition: hypertension
Age Group: adult
Sex: M+F
Population Size: 503
Sources:
Disc. AE: Ischemia, Myocardial infarction...
AEs leading to
discontinuation/dose reduction:
Ischemia (13.6%)
Myocardial infarction (grade 5, 2 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Ischemia 13.6%
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Co-administed with::
atenolol(50 mg four times daily)
Sources:
unhealthy, adult
n = 503
Health Status: unhealthy
Condition: hypertension
Age Group: adult
Sex: M+F
Population Size: 503
Sources:
Myocardial infarction grade 5, 2 patients
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Co-administed with::
atenolol(50 mg four times daily)
Sources:
unhealthy, adult
n = 503
Health Status: unhealthy
Condition: hypertension
Age Group: adult
Sex: M+F
Population Size: 503
Sources:
Overview

Overview

OverviewOther

Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
The hypotensive effect of nisoldipine in renovascular hypertensive rats.
1986 Dec
Alteration of left ventricular diastolic filling in hypertensive patients: effects of nitrendipine and atenolol.
1986 Sep
Renal effects of 1,4-dihydropyridines in animal models of hypertension and renal failure.
1987
Comparative antianginal effects of nisoldipine and nifedipine in patients with chronic stable angina.
1987 Feb
Effects of nisoldipine on left ventricular function during exercise or cold pressor stress.
1987 Nov
Differential effects of 1,4-dihydropyridine calcium channel blockers: therapeutic implications.
1987 Nov
Monotherapy with the calcium channel antagonist nisoldipine for systemic hypertension and comparison with diuretic drugs.
1987 Sep 15
The acute effects of intravenous nisoldipine on left ventricular function 24 to 72 hours after uncomplicated acute myocardial infarction.
1988 Dec
Nisoldipine. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of angina pectoris, hypertension and related cardiovascular disorders.
1988 Dec
The initial hemodynamic response to newer antihypertensive agents at rest and during exercise: review of visacor, doxazosin, nisoldipine, tiapamil, perindoprilat, pinacidil, dilevalol, and carvedilol.
1990 Aug
Effects of nisoldipine on stress-induced changes in haemodynamics and plasma catecholamines in normotensives and hypertensives.
1990 Dec
[Responses of plasma eicosanoids and hemodynamics to myocardial ischemia and the salutary effect of calcium entry blocker].
1990 Feb
Hemodynamic mechanisms of antianginal action of calcium channel blocker nisoldipine in dynamic exercise-induced angina.
1990 Jun
Usefulness of oral nisoldipine for stable angina pectoris. The Nisoldipine Multicenter Angina Study Group.
1991 Oct 15
The acute effects of intravenous nisoldipine on left ventricular function within 24 h after acute myocardial infarction.
1992 Dec
Improved diastolic function with the calcium antagonist nisoldipine (coat-core) in patients post myocardial infarction: results of the DEFIANT study. Doppler Flow and Echocardiography in Functional cardiac Insufficiency: Assessment of Nisoldipine Therapy.
1992 Nov
Cardiovascular effects of nisoldipine in essential hypertension.
1994 Feb
Acute effects of intravenous nisoldipine on left ventricular function after acute myocardial infarction.
1994 May
The effects of nisoldipine on carotid artery stiffness and left ventricular functions.
1995 Sep
Nisoldipine improves ventricular function in rats with ischemic heart failure.
1995 Sep
Nisoldipine CC: clinical experience in hypertension.
1997
Effects of nisoldipine on cytosolic calcium, platelet aggregation, and coagulation/fibrinolysis in patients with coronary artery disease.
1997 Jun
Effects of nisoldipine and/or enalapril on left ventricular function and exercise capacity in patients with recent anterior myocardial infarction and mild cardiac dysfunction.
1997 Mar
Efficacy and tolerability of nisoldipine coat-core formulation in the treatment of essential hypertension: The South African Multicenter ANCHOR Study. Ambulatory Nisoldipine Coat-Core Hypertension Outpatient Response (ANCHOR) Investigators.
1997 Mar
Nisoldipine CC and lisinopril alone or in combination for treatment of mild to moderate systemic hypertension. Canadian Nisoldipine CC Hypertension Trial Group.
1997 Sep
New evidence on the prevention of cardiovascular events in hypertensive patients with type 2 diabetes.
1998
Protective effect of nisoldipine on dipyridamole-induced myocardial ischemia: correlation with exercise electrocardiography.
1998
Nisoldipine selectively induces coronary vasodilation and improves mild myocardial ischemia in dogs: a potential role of cellular acidosis.
1998 Dec
Differential effects of morning and evening dosing of nisoldipine ER on circadian blood pressure and heart rate.
1999 Aug
Rapid-release and coat-core formulations of nisoldipine in treatment of hypertension, angina, and heart failure.
1999 Nov-Dec
Functional embryonic cardiomyocytes after disruption of the L-type alpha1C (Cav1.2) calcium channel gene in the mouse.
2000 Dec 15
Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions.
2000 Feb-Mar
Interaction of digoxin with antihypertensive drugs via MDR1.
2002 Feb 15
Intensive blood pressure control reduces the risk of cardiovascular events in patients with peripheral arterial disease and type 2 diabetes.
2003 Feb 11
Block of cardiac delayed-rectifier and inward-rectifier K+ currents by nisoldipine.
2003 Nov
Enhanced expression of L-type Cav1.3 calcium channels in murine embryonic hearts from Cav1.2-deficient mice.
2003 Oct 17
Comparative efficacy and safety of nisoldipine extended-release (ER) and amlodipine (CESNA-III study) in African American patients with hypertension.
2003 Sep
Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.
2004 Oct 1
The effect of beta-carotene on the photostability of nisoldipine.
2005 Apr
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Pharmacokinetics of oral doses of telmisartan and nisoldipine, given alone and in combination, in patients with essential hypertension.
2007 Mar
Calcium channel blocker-associated small bowel angioedema.
2009 Apr
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.
2013 Sep 5
Patents

Sample Use Guides

The dosage of SULAR (nisoldipine tablet, film coated, extended release) must be adjusted to each patient's needs. Therapy usually should be initiated with 17 mg orally once daily, then increased by 8.5 mg per week or longer intervals, to attain adequate control of blood pressure. Usual maintenance dosage is 17 to 34 mg once daily. Blood pressure response increases over the 8.5 - 34 mg daily dose range but adverse event rates also increase. Doses beyond 34 mg once daily are not recommended. SULAR has been used safely with diuretics, ACE inhibitors, and beta-blocking agents. Patients over age 65, or patients with impaired liver function are expected to develop higher plasma concentrations of nisoldipine. Their blood pressure should be monitored closely during any dosage adjustment. A starting dose not exceeding 8.5 mg daily is recommended in these patient groups. SULAR tablets should be administered orally once daily. SULAR should be taken on an empty stomach (1 hour before or 2 hours after a meal). Grapefruit products should be avoided before and after dosing. SULAR is an extended release dosage form and tablets should be swallowed whole, not bitten, divided or crushed.
Route of Administration: Oral
Nisoldipine depressed in a dose dependent manner the spontaneous rhythmic contractions displayed by the human coronary artery preparations and at 1 nM abolished these contractions. Nisoldipine was twenty times more potent than nifedipine as an inhibitor of increase in tone induced by depolarization (100 mM K+). The rhythmic activity induced by serotonin (10μM) was more sensitive to nisoldipine than to nifedipine.
Substance Class Chemical
Created
by admin
on Fri Jun 25 22:03:46 UTC 2021
Edited
by admin
on Fri Jun 25 22:03:46 UTC 2021
Record UNII
4I8HAB65SZ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NISOLDIPINE
INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
NISOLDIPINE [MART.]
Common Name English
3,5-PYRIDINEDICARBOXYLIC ACID, 1,4-DIHYDRO-2,6-DIMETHYL-4-(2-NITROPHENYL)-, METHYL 2-METHYLPROPYL ESTER, (+/-)-
Common Name English
NISOLDIPINE [ORANGE BOOK]
Common Name English
3,5-PYRIDINEDICARBOXYLIC ACID, 1,4-DIHYDRO-2,6-DIMETHYL-4-(2-NITROPHENYL)-, 3-METHYL 5-(2-METHYLPROPYL) ESTER
Systematic Name English
NISOLDIPIN
Brand Name English
BAYMYCARD
Brand Name English
SULAR
Brand Name English
NISOCOR
Brand Name English
(+/-)-NISOLDIPINE
Common Name English
NISOLDIPINE [JAN]
Common Name English
NISOLDIPINE [INN]
Common Name English
NISOLDIPINE [USAN]
Common Name English
METHYL 2-METHYLPROPYL-1,4-DIHYDRO-2,6-DIMETHYL-4-(2-NITROPHENYL)-3,5-PYRIDINEDICARBOXYLATE, DL-
Common Name English
(+/-)-BAY-K-5552
Common Name English
NISOLDIPINE [VANDF]
Common Name English
NISOLDIPINE [WHO-DD]
Common Name English
NSC-759106
Code English
NISOLDIPINE (STN)
Brand Name English
NISOLDIPINE [USP-RS]
Common Name English
NISOLDIPINE [MI]
Common Name English
BAY-K-5552
Code English
GEOMATRIX 16E
Brand Name English
BAY K 5552
Code English
3,5-PYRIDINEDICARBOXYLIC ACID, 1,4-DIHYDRO-2,6-DIMETHYL-4-(2-NITROPHENYL)-, METHYL 2-METHYLPROPYL ESTER
Common Name English
Classification Tree Code System Code
WHO-VATC QC08CA07
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
NCI_THESAURUS C333
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
NDF-RT N0000175421
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
WHO-ATC C08CA07
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
LIVERTOX 688
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
Code System Code Type Description
MERCK INDEX
M7921
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
PRIMARY Merck Index
ECHA (EC/EINECS)
264-407-7
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PRIMARY
MESH
D015737
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
PRIMARY
LACTMED
Nisoldipine
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
PRIMARY
INN
4753
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
PRIMARY
NDF-RT
N0000178477
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
PRIMARY Decreased Blood Pressure [PE]
DRUG BANK
DB00401
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PRIMARY
ChEMBL
CHEMBL1726
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PRIMARY
USP_CATALOG
1463927
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PRIMARY USP-RS
EVMPD
SUB09307MIG
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PRIMARY
EPA CompTox
63675-72-9
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
PRIMARY
RXCUI
7435
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
PRIMARY RxNorm
DRUG CENTRAL
1942
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PRIMARY
IUPHAR
2524
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PRIMARY
FDA UNII
4I8HAB65SZ
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PRIMARY
NCI_THESAURUS
C29291
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
PRIMARY
PUBCHEM
4499
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
PRIMARY
WIKIPEDIA
NISOLDIPINE
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
PRIMARY
CAS
63675-72-9
Created by admin on Fri Jun 25 22:03:46 UTC 2021 , Edited by admin on Fri Jun 25 22:03:46 UTC 2021
PRIMARY
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