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
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 |
---|---|---|---|---|
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 |
---|---|---|
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 |
|
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 Nov |
|
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 |
|
The place of isradipine in the treatment of hypertension. | 1991 Feb |
|
Low-dose isradipine once daily effectively controls 24-h blood pressure in essential hypertension. | 1991 Feb |
|
MIDAS, the Multicenter Isradipine/Diuretic Atherosclerosis Study. Design features and baseline data. | 1991 Feb |
|
The calcium antagonist PN 200-110 inhibits the reinforcing properties of cocaine. | 1991 Mar |
|
MIDAS: hypertension and atherosclerosis. A trial of the effects of antihypertensive drug treatment on atherosclerosis. MIDAS Research Group. | 1992 |
|
[Multicenter study of isradipine in the treatment of hypertension]. | 1992 Apr |
|
Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel. | 1992 Jan 25 |
|
Isradipine treatment for hypertension in general practice in Hong Kong. | 1992 Jun |
|
How to study the role of hypertension in atherosclerosis. Lessons from MIDAS. Multicentre Isradipine Diuretic Atherosclerosis Study. | 1996 |
|
Contrasting effects of calcium channel blockade versus converting enzyme inhibition on proteinuria in African Americans with non-insulin-dependent diabetes mellitus and nephropathy. | 1997 May |
|
Isradipine in prediabetic hypertensive subjects. | 1998 Dec |
|
Responding for rewarding brain stimulation: cocaine and isradipine plus naltrexone. | 1998 Oct |
|
An open trial comparing isradipine with hydralazine and methyl dopa in the treatment of patients with severe pre-eclampsia. | 1999 May |
|
Hypertension after liver transplantation: a predictive role for pretreatment hemodynamics and effects of isradipine on the systemic and renal circulations. | 2000 Mar |
|
Treatment advances for cocaine-induced ischemic stroke: focus on dihydropyridine-class calcium channel antagonists. | 2001 Aug |
|
Life-threatening isradipine poisoning in a child. | 2002 Jun |
|
Functional characterization of the L-type Ca2+ channel Cav1.4alpha1 from mouse retina. | 2004 Feb |
|
Calcium channels are involved in calcium oxalate crystal formation in specialized cells of Pistia stratiotes L. | 2004 Jun |
|
Proliferation of cultured human gingival fibroblasts caused by isradipine, a dihydropyridine-derivative calcium antagonist. | 2004 Jun 30 |
|
Isoform-specific regulation of mood behavior and pancreatic beta cell and cardiovascular function by L-type Ca 2+ channels. | 2004 May |
|
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance. | 2004 Nov |
|
Comparison of blood pressure control with amlodipine and controlled-release isradipine: an open-label, drug substitution study. | 2005 Apr |
|
Isradipine decreases the hemodynamic response of cocaine and methamphetamine results from two human laboratory studies: results from two human laboratory studies. | 2005 Jun |
|
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 |
|
Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. | 2009 Feb |
|
Antagonizing L-type Ca2+ channel reduces development of abnormal involuntary movement in the rat model of L-3,4-dihydroxyphenylalanine-induced dyskinesia. | 2009 Mar 15 |
|
Blocking L-type calcium channels reduced the threshold of cAMP-induced steroidogenic acute regulatory gene expression in MA-10 mouse Leydig cells. | 2010 Jan |
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
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Code | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
NDF-RT |
N0000007556
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
||
|
NCI_THESAURUS |
C333
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
||
|
WHO-ATC |
C08CA03
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
||
|
NDF-RT |
N0000000069
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
||
|
WHO-VATC |
QC08CA03
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
||
|
LIVERTOX |
NBK548193
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
||
|
NDF-RT |
N0000175421
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
DB00270
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
100000091633
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
SUB08346MIG
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
33910
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | RxNorm | ||
|
YO1UK1S598
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
D017275
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
1511
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
Isradipine
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
Z-3
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
C47577
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
3784
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
m6557
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | Merck Index | ||
|
CHEMBL1648
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
4488
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
75695-93-1
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
5724
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
ISRADIPINE
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
YO1UK1S598
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
759892
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
1354207
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY | |||
|
DTXSID4023179
Created by
admin on Fri Dec 15 17:32:20 GMT 2023 , Edited by admin on Fri Dec 15 17:32:20 GMT 2023
|
PRIMARY |
ACTIVE MOIETY