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

Details

Stereochemistry RACEMIC
Molecular Formula C19H21N3O5
Molecular Weight 371.3871
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ISRADIPINE

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

HIDE SMILES / InChI

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.

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

2015
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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
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
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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
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
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
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
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 Mon Mar 31 18:47:53 GMT 2025
Edited
by admin
on Mon Mar 31 18:47:53 GMT 2025
Record UNII
YO1UK1S598
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DYNACIRC
Preferred Name English
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
Isradipine [WHO-DD]
Common Name English
ISRADIPINE [MI]
Common Name English
ISRADIPINE [EP MONOGRAPH]
Common Name English
PN-200-110
Code English
ISRADIPINE [MART.]
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 Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
NCI_THESAURUS C333
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
WHO-ATC C08CA03
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
NDF-RT N0000000069
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
WHO-VATC QC08CA03
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
LIVERTOX NBK548193
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
NDF-RT N0000175421
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
Code System Code Type Description
DRUG BANK
DB00270
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
PRIMARY
SMS_ID
100000091633
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
PRIMARY
EVMPD
SUB08346MIG
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PRIMARY
RXCUI
33910
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PRIMARY RxNorm
DAILYMED
YO1UK1S598
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
PRIMARY
MESH
D017275
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PRIMARY
DRUG CENTRAL
1511
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PRIMARY
LACTMED
Isradipine
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PRIMARY
USAN
Z-3
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PRIMARY
NCI_THESAURUS
C47577
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
PRIMARY
PUBCHEM
3784
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PRIMARY
MERCK INDEX
m6557
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
PRIMARY Merck Index
ChEMBL
CHEMBL1648
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PRIMARY
IUPHAR
4488
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
PRIMARY
CAS
75695-93-1
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PRIMARY
INN
5724
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PRIMARY
WIKIPEDIA
ISRADIPINE
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
PRIMARY
FDA UNII
YO1UK1S598
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
PRIMARY
NSC
759892
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
PRIMARY
RS_ITEM_NUM
1354207
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
PRIMARY
EPA CompTox
DTXSID4023179
Created by admin on Mon Mar 31 18:47:53 GMT 2025 , Edited by admin on Mon Mar 31 18:47:53 GMT 2025
PRIMARY
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