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 Date2015 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
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 |
|---|---|---|
| Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: a study to assess the drug's cardiac ion channel profile. | 2013-12-01 |
|
| Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). | 2013-12 |
|
| Blocking L-type calcium channels reduced the threshold of cAMP-induced steroidogenic acute regulatory gene expression in MA-10 mouse Leydig cells. | 2010-01 |
|
| Calcium channel blocker-associated small bowel angioedema. | 2009-04 |
|
| Antagonizing L-type Ca2+ channel reduces development of abnormal involuntary movement in the rat model of L-3,4-dihydroxyphenylalanine-induced dyskinesia. | 2009-03-15 |
|
| Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. | 2009-02 |
|
| Calcium antagonist isradipine-induced calcium influx through nonselective cation channels in human gingival fibroblasts. | 2006-03-27 |
|
| Isradipine decreases the hemodynamic response of cocaine and methamphetamine results from two human laboratory studies: results from two human laboratory studies. | 2005-06 |
|
| Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects. | 2005-06 |
|
| Comparison of blood pressure control with amlodipine and controlled-release isradipine: an open-label, drug substitution study. | 2005-04 |
|
| Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance. | 2004-11 |
|
| Proliferation of cultured human gingival fibroblasts caused by isradipine, a dihydropyridine-derivative calcium antagonist. | 2004-06-30 |
|
| Calcium channels are involved in calcium oxalate crystal formation in specialized cells of Pistia stratiotes L. | 2004-06 |
|
| Isoform-specific regulation of mood behavior and pancreatic beta cell and cardiovascular function by L-type Ca 2+ channels. | 2004-05 |
|
| Functional characterization of the L-type Ca2+ channel Cav1.4alpha1 from mouse retina. | 2004-02 |
|
| An open trial comparing isradipine with hydralazine and methyl dopa in the treatment of patients with severe pre-eclampsia. | 1999-05 |
|
| Isradipine in prediabetic hypertensive subjects. | 1998-12 |
|
| Responding for rewarding brain stimulation: cocaine and isradipine plus naltrexone. | 1998-10 |
|
| Contrasting effects of calcium channel blockade versus converting enzyme inhibition on proteinuria in African Americans with non-insulin-dependent diabetes mellitus and nephropathy. | 1997-05 |
|
| Blood pressure and metabolic responses to moderate sodium restriction in isradipine-treated hypertensive patients. | 1997-01 |
|
| Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial. | 1996-09-11 |
|
| Trials investigating the anti-atherosclerotic effects of antihypertensive drugs. | 1996-09 |
|
| Effects of calcium entry blockers on distribution of blood volume. | 1996-07 |
|
| How to study the role of hypertension in atherosclerosis. Lessons from MIDAS. Multicentre Isradipine Diuretic Atherosclerosis Study. | 1996 |
|
| The antiatherosclerotic effect of calcium antagonists in man--what did MIDAS actually show? Multicenter Isradipine Diuretic Atherosclerosis Study. | 1995-05 |
|
| Isradipine. An update of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of mild to moderate hypertension. | 1995-04 |
|
| Calcium-channel entry blocker therapy for hypertensive patients with concomitant renal impairment: a focus on isradipine. | 1994-12 |
|
| A large, prospective, open-label study of isradipine in patients with essential hypertension. The Isradipine Investigators Group. | 1994-07-01 |
|
| Duration of effects of isradipine during twice daily therapy in angina pectoris. | 1994-04 |
|
| MIDAS: rationale, design and descriptive data of trial patients. The MIDAS Research Group. | 1994 |
|
| Disparate cardiovascular response to stress tests during isradipine and fosinopril therapy. | 1993-09-01 |
|
| Obesity as a determinant for response to antihypertensive treatment. | 1993-08-28 |
|
| [The antihypertensive effect of isradipine and additional pharmacodynamic effects]. | 1993-03 |
|
| A multicenter comparison of isradipine and felodipine in the treatment of mild-to-moderate hypertension. The Physician's Study Group. | 1993-03 |
|
| Parenteral isradipine reduces blood pressure in hypertensive crisis. | 1993-03 |
|
| Carotid plaque associations among hypertensive patients. | 1993-02-22 |
|
| A randomized comparative study of the electrophysiological and electrocardiographic effects of isradipine vs verapamil. | 1993 |
|
| The calcium antagonist PN 200-110 inhibits the reinforcing properties of cocaine. | 1991-03 |
|
| The place of isradipine in the treatment of hypertension. | 1991-02 |
|
| Low-dose isradipine once daily effectively controls 24-h blood pressure in essential hypertension. | 1991-02 |
|
| MIDAS, the Multicenter Isradipine/Diuretic Atherosclerosis Study. Design features and baseline data. | 1991-02 |
|
| Effect of long-term isradipine treatment on the hypertension-dependent changes in coronary arteries in spontaneously hypertensive rats. | 1991 |
|
| The Multicenter Isradipine/Diuretic Atherosclerosis Study: a study of the antiatherogenic properties of isradipine in hypertensive patients. MIDAS Research Group. | 1991 |
|
| Antiischemic and hemodynamic effects of intravenous isradipine, a new calcium antagonist, in coronary heart disease: a comparative double-blind cross-over study with nifedipine. | 1990-11 |
|
| Antihypertensive effect of isradipine administered once or twice daily on ambulatory blood pressure. | 1990-02-15 |
|
| The new calcium antagonist isradipine. Effect on blood pressure and the left ventricle in black hypertensive patients. | 1990-01 |
|
| A comparison of antihypertensive drug effects on the progression of extracranial carotid atherosclerosis. The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). | 1990 |
|
| Multicenter study with isradipine and diuretics against atherosclerosis. US MIDAS Research Group. | 1990 |
|
| Evaluation of the safety and efficacy of isradipine in elderly patients with essential hypertension. The British Isradipine Hypertension Group. | 1989-04-17 |
|
| Acute calcium entry blockade inhibits the blood pressure but not the hormonal responses to angiotensin II. | 1989 |
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
Mon Mar 31 18:47:53 GMT 2025
by
admin
on
Mon Mar 31 18:47:53 GMT 2025
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| Record UNII |
YO1UK1S598
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| Record Status |
Validated (UNII)
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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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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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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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TARGET -> INHIBITOR |
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ACTIVE MOIETY |