U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C19H21N3O5
Molecular Weight 371.3879
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ISRADIPINE

SMILES

CC(C)OC(=O)C1=C(C)NC(=C(C1c2cccc3c2non3)C(=O)OC)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

HIDE SMILES / InChI

Molecular Formula C19H21N3O5
Molecular Weight 371.3879
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ISRADIPINE

Approved Use

Isradipine capsules are indicated in the management of hypertension. It may be used alone or concurrently with thiazide-type diuretics.

Launch Date

1.44858245E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
11.44 ng/mL
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
14.52 ng × h/mL
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
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
2.85 h
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
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
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

Doses

DosePopulationAdverse events​
30 mg single, oral
Highest studied dose
Dose: 30 mg
Route: oral
Route: single
Dose: 30 mg
Sources:
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
Leg edema
Dizziness
Sources: Page: p.1823, 1826, 1827
100 mg single, oral (max)
Overdose
healthy
Other AEs: Lethargy, Sinus tachycardia...
200 mg single, oral
Overdose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Co-administed with::
ethanol
Sources:
healthy
Other AEs: Flushing, Tachycardia...
Other AEs:
Flushing
Tachycardia
Electrocardiogram ST segment depression
Hypotension
Sources:
AEs

AEs

AESignificanceDosePopulation
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
healthy
Lethargy
100 mg single, oral (max)
Overdose
healthy
Sinus tachycardia
100 mg single, oral (max)
Overdose
healthy
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
Flushing
200 mg single, oral
Overdose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Co-administed with::
ethanol
Sources:
healthy
Hypotension
200 mg single, oral
Overdose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Co-administed with::
ethanol
Sources:
healthy
Tachycardia
200 mg single, oral
Overdose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Co-administed with::
ethanol
Sources:
healthy
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
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
Multicenter study with isradipine and diuretics against atherosclerosis. US MIDAS Research Group.
1990
Antihypertensive effect of isradipine administered once or twice daily on ambulatory blood pressure.
1990 Feb 15
The new calcium antagonist isradipine. Effect on blood pressure and the left ventricle in black hypertensive patients.
1990 Jan
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
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
A randomized comparative study of the electrophysiological and electrocardiographic effects of isradipine vs verapamil.
1993
Obesity as a determinant for response to antihypertensive treatment.
1993 Aug 28
Carotid plaque associations among hypertensive patients.
1993 Feb 22
[The antihypertensive effect of isradipine and additional pharmacodynamic effects].
1993 Mar
A multicenter comparison of isradipine and felodipine in the treatment of mild-to-moderate hypertension. The Physician's Study Group.
1993 Mar
Parenteral isradipine reduces blood pressure in hypertensive crisis.
1993 Mar
Disparate cardiovascular response to stress tests during isradipine and fosinopril therapy.
1993 Sep 1
MIDAS: rationale, design and descriptive data of trial patients. The MIDAS Research Group.
1994
Calcium-channel entry blocker therapy for hypertensive patients with concomitant renal impairment: a focus on isradipine.
1994 Dec
A large, prospective, open-label study of isradipine in patients with essential hypertension. The Isradipine Investigators Group.
1994 Jul-Aug
The antiatherosclerotic effect of calcium antagonists in man--what did MIDAS actually show? Multicenter Isradipine Diuretic Atherosclerosis Study.
1995 May
How to study the role of hypertension in atherosclerosis. Lessons from MIDAS. Multicentre Isradipine Diuretic Atherosclerosis Study.
1996
Effects of calcium entry blockers on distribution of blood volume.
1996 Jul
Trials investigating the anti-atherosclerotic effects of antihypertensive drugs.
1996 Sep
Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial.
1996 Sep 11
Blood pressure and metabolic responses to moderate sodium restriction in isradipine-treated hypertensive patients.
1997 Jan
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
Cav1.4alpha1 subunits can form slowly inactivating dihydropyridine-sensitive L-type Ca2+ channels lacking Ca2+-dependent inactivation.
2003 Jul 9
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
Blocking L-type calcium channels reduced the threshold of cAMP-induced steroidogenic acute regulatory gene expression in MA-10 mouse Leydig cells.
2010 Jan
Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11).
2013 Dec
Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: a study to assess the drug's cardiac ion channel profile.
2013 Dec 1
Patents

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
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 Fri Jun 25 21:01:48 UTC 2021
Edited
by admin
on Fri Jun 25 21:01:48 UTC 2021
Record UNII
YO1UK1S598
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ISRADIPINE
EP   INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
ISOPROPYL METHYL (+/-)-4-(4-BENZOFURAZANYL)-1,4-DIHYDRO-2,6-DIMETHYL-3,5-PYRIDINEDICARBOXYLATE
Systematic Name English
ISRADIPINE [USP MONOGRAPH]
Common Name English
ISRADIPINE [USP-RS]
Common Name English
ISRADIPINE [INN]
Common Name English
DYNACIRC
Brand Name English
ISRADIPINE [MI]
Common Name English
ISRADIPINE [EP MONOGRAPH]
Common Name English
PN-200-110
Code English
ISRADIPINE [MART.]
Common Name English
ISRADIPINE [WHO-DD]
Common Name English
ISRADIPINE [VANDF]
Common Name English
3,5-PYRIDINEDICARBOXYLIC ACID, 4-(4-BENZOFURAZANYL)-1,4-DIHYDRO-2,6-DIMETHYL-, METHYL 1-METHYLETHYL ESTER, (+/-)-
Common Name English
ISRADIPINE [USAN]
Common Name English
ISRADIPINE [ORANGE BOOK]
Common Name English
NSC-759892
Code English
PN 200-110
Code English
Classification Tree Code System Code
NDF-RT N0000007556
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
NCI_THESAURUS C333
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
WHO-ATC C08CA03
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
NDF-RT N0000000069
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
WHO-VATC QC08CA03
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
LIVERTOX 524
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
NDF-RT N0000175421
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
Code System Code Type Description
DRUG BANK
DB00270
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY
USP_CATALOG
1354207
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY USP-RS
EVMPD
SUB08346MIG
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY
RXCUI
33910
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY RxNorm
MESH
D017275
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY
DRUG CENTRAL
1511
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY
LACTMED
Isradipine
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY
NCI_THESAURUS
C47577
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY
PUBCHEM
3784
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY
MERCK INDEX
M6557
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL1648
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY
IUPHAR
4488
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY
CAS
75695-93-1
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY
INN
5724
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY
WIKIPEDIA
ISRADIPINE
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY
FDA UNII
YO1UK1S598
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY
EPA CompTox
75695-93-1
Created by admin on Fri Jun 25 21:01:48 UTC 2021 , Edited by admin on Fri Jun 25 21:01:48 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY