Details
Stereochemistry | RACEMIC |
Molecular Formula | C19H21N3O5 |
Molecular Weight | 371.3871 |
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=CC=CC3=NON=C23)C(=O)OC(C)C
InChI
InChIKey=HMJIYCCIJYRONP-UHFFFAOYSA-N
InChI=1S/C19H21N3O5/c1-9(2)26-19(24)15-11(4)20-10(3)14(18(23)25-5)16(15)12-7-6-8-13-17(12)22-27-21-13/h6-9,16,20H,1-5H3
Molecular Formula | C19H21N3O5 |
Molecular Weight | 371.3871 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
Isradipine (tradenames DynaCirc, Prescal) is a calcium channel blocker of the dihydropyridine class. It is usually prescribed for the treatment of high blood pressure in order to reduce the risk of stroke and heart attack. Except for diuretic activity, the mechanism of which is not clearly understood, the pharmacodynamics effects of isradipine observed in whole animals can also be explained by calcium channel blocking activity, especially dilating effects in arterioles, which reduce systemic resistance and lower blood pressure, with a small increase in resting heart rate. Isradipine binds to calcium channels with high affinity and specificity and inhibits calcium flux into cardiac and arterial smooth muscle cells. It exhibits greater selectivity towards arterial smooth muscle cells owing to alternative splicing of the alpha-1 subunit of the channel and increased prevalence of inactive channels in smooth muscle cells. Although like other dihydropyridine calcium channel blockers, isradipine has negative inotropic effects in vitro; studies conducted in intact anesthetized animals have shown that the vasodilating effect occurs at doses lower than those do which affect contractility. In patients with normal ventricular function, isradipine's afterload reducing properties lead to some increase in cardiac output. Effects in patients with impaired ventricular function have not been fully studied. Most adverse reactions were mild and related to the vasodilatory effects of isradipine (dizziness, edema, palpitations, flushing, tachycardia), and many were transient. About 5% of isradipine patients left studies prematurely because of adverse reactions (vs. 3% of placebo patients and 6% of active control patients), principally due to headache, edema, dizziness, palpitations, and gastrointestinal disturbances.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2095229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10766758 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ISRADIPINE Approved UseIsradipine capsules are indicated in the management of hypertension. It may be used alone or concurrently with thiazide-type diuretics. Launch Date1.44858245E12 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
11.44 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2965165/ |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
ISRADIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
29.84 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2965165/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
ISRADIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
5.89 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2965165/ |
2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
ISRADIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
14.52 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2965165/ |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
ISRADIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
31.01 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2965165/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
ISRADIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
7.31 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2965165/ |
2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
ISRADIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.85 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2965165/ |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
ISRADIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
2.68 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2965165/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
ISRADIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
2.93 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2965165/ |
2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
ISRADIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
30 mg single, oral Highest studied dose |
healthy, 27 - 44 n = 8 Health Status: healthy Age Group: 27 - 44 Sex: M Population Size: 8 Sources: |
|
0.015 mg/kg single, intravenous Highest studied dose Dose: 0.015 mg/kg Route: intravenous Route: single Dose: 0.015 mg/kg Sources: Page: p.1103 |
unhealthy, 58+/-8 n = 8 Health Status: unhealthy Condition: Chest pain| stable angina Age Group: 58+/-8 Sex: M Population Size: 8 Sources: Page: p.1103 |
|
10 mg 1 times / day multiple, oral MTD Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: Page: p.1823, 1826, 1827 |
unhealthy, 58.5 n = 26 Health Status: unhealthy Condition: Parkinson's disease Age Group: 58.5 Sex: M+F Population Size: 26 Sources: Page: p.1823, 1826, 1827 |
Disc. AE: Drop of blood pressure, Leg edema... AEs leading to discontinuation/dose reduction: Drop of blood pressure Sources: Page: p.1823, 1826, 1827Leg edema Dizziness |
100 mg single, oral (max) Overdose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: |
healthy Health Status: healthy Sources: |
Other AEs: Lethargy, Sinus tachycardia... Other AEs: Lethargy Sources: Sinus tachycardia Hypotension |
200 mg single, oral Overdose Dose: 200 mg Route: oral Route: single Dose: 200 mg Co-administed with:: ethanol Sources: |
healthy Health Status: healthy Sources: |
Other AEs: Flushing, Tachycardia... Other AEs: Flushing Sources: Tachycardia Electrocardiogram ST segment depression Hypotension |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Dizziness | Disc. AE | 10 mg 1 times / day multiple, oral MTD Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: Page: p.1823, 1826, 1827 |
unhealthy, 58.5 n = 26 Health Status: unhealthy Condition: Parkinson's disease Age Group: 58.5 Sex: M+F Population Size: 26 Sources: Page: p.1823, 1826, 1827 |
Drop of blood pressure | Disc. AE | 10 mg 1 times / day multiple, oral MTD Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: Page: p.1823, 1826, 1827 |
unhealthy, 58.5 n = 26 Health Status: unhealthy Condition: Parkinson's disease Age Group: 58.5 Sex: M+F Population Size: 26 Sources: Page: p.1823, 1826, 1827 |
Leg edema | Disc. AE | 10 mg 1 times / day multiple, oral MTD Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: Page: p.1823, 1826, 1827 |
unhealthy, 58.5 n = 26 Health Status: unhealthy Condition: Parkinson's disease Age Group: 58.5 Sex: M+F Population Size: 26 Sources: Page: p.1823, 1826, 1827 |
Hypotension | 100 mg single, oral (max) Overdose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: |
healthy Health Status: healthy Sources: |
|
Lethargy | 100 mg single, oral (max) Overdose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: |
healthy Health Status: healthy Sources: |
|
Sinus tachycardia | 100 mg single, oral (max) Overdose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: |
healthy Health Status: healthy Sources: |
|
Electrocardiogram ST segment depression | 200 mg single, oral Overdose Dose: 200 mg Route: oral Route: single Dose: 200 mg Co-administed with:: ethanol Sources: |
healthy Health Status: healthy Sources: |
|
Flushing | 200 mg single, oral Overdose Dose: 200 mg Route: oral Route: single Dose: 200 mg Co-administed with:: ethanol Sources: |
healthy Health Status: healthy Sources: |
|
Hypotension | 200 mg single, oral Overdose Dose: 200 mg Route: oral Route: single Dose: 200 mg Co-administed with:: ethanol Sources: |
healthy Health Status: healthy Sources: |
|
Tachycardia | 200 mg single, oral Overdose Dose: 200 mg Route: oral Route: single Dose: 200 mg Co-administed with:: ethanol Sources: |
healthy Health Status: healthy Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/11560876/ Page: - |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/11560876/ Page: - |
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/11487504/ Page: - |
||||
Sources: https://pubmed.ncbi.nlm.nih.gov/12007180/ Page: 1.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Acute calcium entry blockade inhibits the blood pressure but not the hormonal responses to angiotensin II. | 1989 |
|
A comparison of antihypertensive drug effects on the progression of extracranial carotid atherosclerosis. The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). | 1990 |
|
Effect of long-term isradipine treatment on the hypertension-dependent changes in coronary arteries in spontaneously hypertensive rats. | 1991 |
|
Low-dose isradipine once daily effectively controls 24-h blood pressure in essential hypertension. | 1991 Feb |
|
The calcium antagonist PN 200-110 inhibits the reinforcing properties of cocaine. | 1991 Mar |
|
[Multicenter study of isradipine in the treatment of hypertension]. | 1992 Apr |
|
Disparate cardiovascular response to stress tests during isradipine and fosinopril therapy. | 1993 Sep 1 |
|
An open trial comparing isradipine with hydralazine and methyl dopa in the treatment of patients with severe pre-eclampsia. | 1999 May |
|
[Effects of calcium antagonists on atherosclerosis progression and intima media thickness]. | 2000 |
|
Treatment advances for cocaine-induced ischemic stroke: focus on dihydropyridine-class calcium channel antagonists. | 2001 Aug |
|
Functional coupling between 'R-type' Ca2+ channels and insulin secretion in the insulinoma cell line INS-1. | 2001 Feb |
|
alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages. | 2001 Jun 22 |
|
Isradipine enhancement of cerebral blood flow in abstinent cocaine abusers with and without chronic perfusion deficits. | 2002 Summer |
|
Effects of naltrexone and isradipine, alone or in combination, on cocaine responses in humans. | 2003 Jul |
|
Comparison of blood pressure control with amlodipine and controlled-release isradipine: an open-label, drug substitution study. | 2005 Apr |
|
Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects. | 2005 Jun |
|
Calcium antagonist isradipine-induced calcium influx through nonselective cation channels in human gingival fibroblasts. | 2006 Mar 27 |
|
Calcium channel blocker-associated small bowel angioedema. | 2009 Apr |
|
Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: a study to assess the drug's cardiac ion channel profile. | 2013 Dec 1 |
Sample Use Guides
The recommended initial dose of isradipine is 2.5 mg b.i.d. alone or in combination with a thiazide diuretic. An antihypertensive response usually occurs within 2-3 hours. Maximal response may require 2-4 weeks. If a satisfactory reduction in blood pressure does not occur after this period, the dose may be adjusted in increments of 5 mg/day at 2-4 week intervals up to a maximum of 20 mg/day. Most patients, however, show no additional response to doses above 10 mg/day, and adverse effects are increased in frequency above 10 mg/day.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1285938
Curator's Comment: Cytosolic Ca2+ concentration ([Ca2+]i) was investigated in erythrocytes from spontaneously hypertensive rats (SHR) and their normotensive controls (WKY), after an acute treatment with the Ca2+ antagonist isradipine. In vitro, isradipine dose-dependently decreased [Ca2+]i only in SHR (P = .006). The reduction by isradipine of the elevated [Ca2+]i in SHR suggests the presence of a greater dihydropyridine-sensitive Ca2+ influx in the SHR erythrocyte.
Unknown
Substance Class |
Chemical
Created
by
admin
on
Edited
Thu Jul 06 00:51:30 UTC 2023
by
admin
on
Thu Jul 06 00:51:30 UTC 2023
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Record UNII |
YO1UK1S598
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Record Status |
Validated (UNII)
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Record Version |
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-
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000007556
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NCI_THESAURUS |
C333
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WHO-ATC |
C08CA03
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NDF-RT |
N0000000069
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WHO-VATC |
QC08CA03
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LIVERTOX |
NBK548193
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NDF-RT |
N0000175421
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DB00270
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100000091633
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SUB08346MIG
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33910
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YO1UK1S598
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D017275
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1511
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Isradipine
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Z-3
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C47577
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3784
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M6557
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CHEMBL1648
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4488
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75695-93-1
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5724
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ISRADIPINE
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YO1UK1S598
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759892
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1354207
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DTXSID4023179
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
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IMPURITY -> PARENT |
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ACTIVE MOIETY |