Details
Stereochemistry | RACEMIC |
Molecular Formula | C20H24N2O6 |
Molecular Weight | 388.4144 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC(=O)C1=C(C)NC(C)=C(C1C2=C(C=CC=C2)[N+]([O-])=O)C(=O)OCC(C)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
DescriptionCurator'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
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8270166
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
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2095229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3154674 |
0.04 nM [Kd] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | SULAR Approved UseNisoldipine extended-release tablets are indicated for the treatment of hypertension. They may be used alone or in combination with other antihypertensive agents. Launch Date7.916832E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.44 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1634646/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1634646/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
19.06 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1634646/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1634646/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
12.61 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1634646/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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%) Sources: Myocardial infarction (grade 5, 2 patients) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/ Page: - |
yes [Ki 1.97 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/20599790/ Page: - |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/28756727/ Page: - |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/28756727/ Page: - |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/28756727/ Page: - |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/28756727/ Page: - |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/20599790/ Page: - |
yes |
Drug as victim
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/19399628/ Page: - |
PubMed
Title | Date | PubMed |
---|---|---|
Alteration of left ventricular diastolic filling in hypertensive patients: effects of nitrendipine and atenolol. | 1986 Sep |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
A comparison of nisoldipine coat-core and felodipine in the treatment of mild-to-moderate hypertension. | 1998 Jun |
|
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 |
|
Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
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.
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WHO-VATC |
QC08CA07
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NCI_THESAURUS |
C333
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NDF-RT |
N0000175421
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WHO-ATC |
C08CA07
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LIVERTOX |
NBK548364
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m7921
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100000092490
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264-407-7
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D015737
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Nisoldipine
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N0000178477
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DB00401
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1942
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NISOLDIPINE
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63675-72-9
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)