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

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
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
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 Thu Jul 06 00:51:30 UTC 2023
Edited
by admin
on Thu Jul 06 00:51:30 UTC 2023
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 [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 Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
NCI_THESAURUS C333
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
WHO-ATC C08CA03
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
NDF-RT N0000000069
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
WHO-VATC QC08CA03
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
LIVERTOX NBK548193
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
NDF-RT N0000175421
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
Code System Code Type Description
DRUG BANK
DB00270
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
SMS_ID
100000091633
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
EVMPD
SUB08346MIG
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
RXCUI
33910
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY RxNorm
DAILYMED
YO1UK1S598
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
MESH
D017275
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
DRUG CENTRAL
1511
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
LACTMED
Isradipine
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
USAN
Z-3
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
NCI_THESAURUS
C47577
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
PUBCHEM
3784
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
MERCK INDEX
M6557
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY Merck Index
ChEMBL
CHEMBL1648
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
IUPHAR
4488
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
CAS
75695-93-1
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
INN
5724
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
WIKIPEDIA
ISRADIPINE
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
FDA UNII
YO1UK1S598
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
NSC
759892
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
RS_ITEM_NUM
1354207
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
EPA CompTox
DTXSID4023179
Created by admin on Thu Jul 06 00:51:30 UTC 2023 , Edited by admin on Thu Jul 06 00:51:30 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY