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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

Description

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 TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ISRADIPINE

Cmax

ValueDoseCo-administeredAnalytePopulation
11.44 ng/mL
5 mg single, oral
ISRADIPINE plasma
Homo sapiens
29.84 ng/mL
10 mg single, oral
ISRADIPINE plasma
Homo sapiens
5.89 ng/mL
2.5 mg single, oral
ISRADIPINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
14.52 ng × h/mL
5 mg single, oral
ISRADIPINE plasma
Homo sapiens
31.01 ng × h/mL
10 mg single, oral
ISRADIPINE plasma
Homo sapiens
7.31 ng × h/mL
2.5 mg single, oral
ISRADIPINE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
2.85 h
5 mg single, oral
ISRADIPINE plasma
Homo sapiens
2.68 h
10 mg single, oral
ISRADIPINE plasma
Homo sapiens
2.93 h
2.5 mg single, oral
ISRADIPINE plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
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
Unknown