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
Molecular Formula | C20H24N2O6 |
Molecular Weight | 388.4144 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
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 |
|
Comparative antianginal effects of nisoldipine and nifedipine in patients with chronic stable angina. | 1987 Feb |
|
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 |
|
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 |
|
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 |
|
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 |
|
Differential effects of morning and evening dosing of nisoldipine ER on circadian blood pressure and heart rate. | 1999 Aug |
|
Intensive blood pressure control reduces the risk of cardiovascular events in patients with peripheral arterial disease and type 2 diabetes. | 2003 Feb 11 |
|
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 |
|
The effect of beta-carotene on the photostability of nisoldipine. | 2005 Apr |
|
Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
|
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
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on
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Sat Dec 16 17:51:42 UTC 2023
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Record UNII |
4I8HAB65SZ
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Record Status |
Validated (UNII)
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WHO-VATC |
QC08CA07
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NCI_THESAURUS |
C333
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N0000175421
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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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7577
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D015737
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Nisoldipine
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N0000178477
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DB00401
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CHEMBL1726
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1942
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NISOLDIPINE
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63675-72-9
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR | |||
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DEGRADENT -> PARENT | |||
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DEGRADENT -> PARENT |
Related Record | Type | Details | ||
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METABOLITE -> PARENT |
Dehydrogenation step is catalyzed by the cytochrome P450 (CYP) 3A4 enzyme
PLASMA
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METABOLITE -> PARENT |
Dehydrogenation step is catalyzed by the cytochrome P450 (CYP) 3A4 enzyme
PLASMA; URINE
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METABOLITE -> PARENT |
Although M9 showed small pharmacological activity ? qualitatively similar to nisoldipine ? in animal models, it does not contribute significantly to the haemodynamic effects of the drug in humans.
PLASMA
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METABOLITE -> PARENT |
Dehydrogenation step is catalyzed by the cytochrome P450 (CYP) 3A4 enzyme
PLASMA; URINE
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METABOLITE -> PARENT |
PLASMA
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METABOLITE -> PARENT |
URINE
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METABOLITE -> PARENT |
Dehydrogenation step is catalysed by the cytochrome P450 (CYP) 3A4 enzyme
URINE
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IMPURITY -> PARENT | |||
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IMPURITY -> PARENT |
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Excretion | PHARMACOKINETIC |
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Urine BIOLOGICAL |
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Biological Half-life | PHARMACOKINETIC |
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