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

Details

Stereochemistry RACEMIC
Molecular Formula C18H19Cl2NO4
Molecular Weight 384.2543
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FELODIPINE

SMILES

CCOC(=O)C1=C(C)NC(=C(C1c2cccc(c2Cl)Cl)C(=O)OC)C

InChI

InChIKey=RZTAMFZIAATZDJ-UHFFFAOYSA-N
InChI=1S/C18H19Cl2NO4/c1-5-25-18(23)14-10(3)21-9(2)13(17(22)24-4)15(14)11-7-6-8-12(19)16(11)20/h6-8,15,21H,5H2,1-4H3

HIDE SMILES / InChI

Molecular Formula C18H19Cl2NO4
Molecular Weight 384.2543
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment:: https://www.drugs.com/pro/felodipine.html

Felodipine is a long-acting 1,4-dihydropyridine calcium channel blocker (CCB)b. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, felodipine prevents calcium-dependent myocyte contraction and vasoconstriction. Felodipine is the most potent CCB in use and is unique in that it exhibits fluorescent activity. In addition to binding to L-type calcium channels, felodipine binds to a number of calcium-binding proteins, exhibits competitive antagonism of the mineralcorticoid receptor, inhibits the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase, and blocks calcium influx through voltage-gated T-type calcium channels. Felodipine is used to treat mild to moderate essential hypertension.

CNS Activity

Curator's Comment:: Animal studies have demonstrated that felodipine crosses the blood-brain barrier and the placenta.

Approval Year

TargetsConditions
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
23.1 nM
10 mg 2 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: FASTED
6.2 nM
5 mg 2 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
17.1 nM
5 mg 2 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
35.6 nM
10 mg 2 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEHYDROFELODIPINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
100.9 nM × h
10 mg 2 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: FASTED
33.7 nM × h
5 mg 2 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
87.5 nM × h
5 mg 2 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
142 nM × h
10 mg 2 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEHYDROFELODIPINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
23.1 h
10 mg 2 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: FASTED
14.1 h
5 mg 2 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
27.5 h
5 mg 2 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 51.5 (39-68)
Health Status: unhealthy
Age Group: 51.5 (39-68)
Sex: M+F
Sources:
Disc. AE: Headache, Ankle edema...
AEs leading to
discontinuation/dose reduction:
Headache (18%)
Ankle edema (6%)
Flushing (6%)
Nausea (2%)
Palpitation (2%)
Vertigo (2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Headache 18%
Disc. AE
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 51.5 (39-68)
Health Status: unhealthy
Age Group: 51.5 (39-68)
Sex: M+F
Sources:
Nausea 2%
Disc. AE
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 51.5 (39-68)
Health Status: unhealthy
Age Group: 51.5 (39-68)
Sex: M+F
Sources:
Palpitation 2%
Disc. AE
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 51.5 (39-68)
Health Status: unhealthy
Age Group: 51.5 (39-68)
Sex: M+F
Sources:
Vertigo 2%
Disc. AE
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 51.5 (39-68)
Health Status: unhealthy
Age Group: 51.5 (39-68)
Sex: M+F
Sources:
Ankle edema 6%
Disc. AE
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 51.5 (39-68)
Health Status: unhealthy
Age Group: 51.5 (39-68)
Sex: M+F
Sources:
Flushing 6%
Disc. AE
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 51.5 (39-68)
Health Status: unhealthy
Age Group: 51.5 (39-68)
Sex: M+F
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 0.726 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes
yes (co-administration study)
Comment: Co-administration of another extended release formulation of felodipine with itraconazole resulted in approximately 8-fold increase in the AUC, more than 6-fold increase in the Cmax, and 2-fold prolongation in the half-life of felodipine.
Page: 6
PubMed

PubMed

TitleDatePubMed
Renal and cardiovascular effects of acute and chronic administration of felodipine to SHR.
1985 Jul 11
Baroreflex control of renin release in spontaneously hypertensive rats after administration of felodipine.
1987
Catecholamines, renin-angiotensin-aldosterone, and cardiovascular response during exercise following acute and long-term calcium antagonism with felodipine in essential hypertension.
1987 Oct
A double-blind comparison of felodipine and hydrochlorothiazide added to metoprolol to control hypertension.
1988
The influence of infusion rate on the hemodynamic effects of felodipine.
1990 Sep
Felodipine in combination with a beta-adrenoceptor blocker as an effective substitute for triple therapy in severe hypertension. The Australian Felodipine Multicentre Study Group.
1991
Felodipine clinical pharmacokinetics.
1991 Dec
Acute effects on exercise tolerance of felodipine and diltiazem, alone and in combination, in stable effort angina.
1991 Jan
Extended release felodipine in essential hypertension. Variations in blood pressure during whole-day continuous ambulatory recording.
1991 Jan
Felodipine: a new dihydropyridine calcium-channel antagonist.
1991 Nov
Long-term effects of felodipine in patients with reduced renal function.
1992 May
General toxicity of the new calcium antagonist felodipine in dogs.
1993 Jul
A multicenter comparison of isradipine and felodipine in the treatment of mild-to-moderate hypertension. The Physician's Study Group.
1993 Mar
Comparison of effects of felodipine versus hydrochlorothiazide on arterial diameter and pulse-wave velocity in essential hypertension.
1993 Oct 1
Efficacy and tolerability of extended-release felodipine and extended-release nifedipine in patients with mild-to-moderate essential hypertension.
1994 Jul-Aug
Mono- and combination therapy with felodipine or enalapril in elderly patients with systolic hypertension.
1994 Mar
Global efficacy and tolerability of losartan, an angiotensin II subtype 1-receptor antagonist, in the treatment of hypertension.
1996
Losartan potassium: a review of its pharmacology, clinical efficacy and tolerability in the management of hypertension.
1996 May
Felodipine in the treatment of severe refractory hypertension.
1996 Sep
Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group.
1997 Aug 5
Calcium antagonists, a useful additional therapy in treatment resistant hypertension: comparison of felodipine ER and nifedipine Retard by 24-h ambulatory blood pressure monitoring.
1997 Jan
Cardiovascular effects of a low-dose combination of ramipril and felodipine in spontaneously hypertensive rats.
1997 Jun
Benazepril versus felodipine as supplement to bendroflumethiazide: evaluation by office and ambulatory blood pressure.
1998 Apr
Influence of felodipine on experimental seizures and activity of different antiepileptic drugs in mice.
1998 Jan-Feb
Significance of blood pressure levels achieved with felodipine anti-hypertensive treatment on cardiovascular structure and function changes.
1998 Jul
A comparison of nisoldipine coat-core and felodipine in the treatment of mild-to-moderate hypertension.
1998 Jun
Improved tolerability of felodipine compared with amlodipine in elderly hypertensives: a randomised, double-blind study in 535 patients, focusing on vasodilatory adverse events. The International Study Group.
1998 Sep
Low Dose Combination Therapy vs. High Dose Monotherapy in the Management of Hypertension.
1999 Nov
Losartan: a review of its use, with special focus on elderly patients.
2000 Mar
Stroke precipitated by moderate blood pressure reduction.
2000 Nov
Photodistributed felodipine-induced facial telangiectasia.
2001 Aug
Effects of thyroid replacement therapy on arterial blood pressure in patients with hypertension and hypothyroidism.
2002 Apr
The effect of nonsteroidal anti-inflammatory drugs on blood pressure in patients treated with different antihypertensive drugs.
2003 Jan-Feb
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Optimal treatment of obesity-related hypertension: the Hypertension-Obesity-Sibutramine (HOS) study.
2007 Apr 17
A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle.
2010 Feb 23
Cystic fibrosis: a new target for 4-Imidazo[2,1-b]thiazole-1,4-dihydropyridines.
2011 Jun 9
Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11).
2013 Dec
Evaluation of in vitro cytochrome P450 induction and inhibition activity of deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber L.
2013 Oct
Patents

Sample Use Guides

In Vivo Use Guide
Usual Adult Dose for Hypertension
Route of Administration: Oral
In Vitro Use Guide
the maximum contraction to NA in rat vessels exposed to felodipine (0.1 umol/L) was reduced by 37%, and the contraction to K+ (62 mmol/L) was reduced by 84% compared with vehicle-treated arteries.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:02:58 UTC 2021
Edited
by admin
on Fri Jun 25 21:02:58 UTC 2021
Record UNII
OL961R6O2C
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FELODIPINE
EP   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
PLENDIL
Brand Name English
FELODIPINE [USP-RS]
Common Name English
FELODIPINE [MART.]
Common Name English
NSC-760343
Code English
FELODIPINE [VANDF]
Common Name English
3,5-PYRIDINEDICARBOXYLIC ACID 4-(2,3-DICHLOROPHENYL)-1,4-DIHYDRO-2,6-DIMETHYL-, ETHYL METHYL ESTER, (+/-)-
Common Name English
FELODIPINE [WHO-DD]
Common Name English
FELODIPINE [ORANGE BOOK]
Common Name English
FELODIPINE [USAN]
Common Name English
FELODIPINE [EP MONOGRAPH]
Common Name English
FELODIPINE [USP MONOGRAPH]
Common Name English
FELODIPINE [MI]
Common Name English
LEXXEL COMPONENT FELODIPINE
Common Name English
FELODIPINE COMPONENT OF LEXXEL
Common Name English
C08CA02
Code English
H 154/82
Code English
FELODIPINE [INN]
Common Name English
(+/-)-ETHYL METHYL 4-(2,3-DICHLOROPHENYL)-1,4-DIHYDRO-2,6-DIMETHYL-3,5-PYRIDINEDICARBOXYLATE
Systematic Name English
FELODIPINE [JAN]
Common Name English
FELODIPINE [USP]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C333
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
WHO-ATC C08CA02
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
WHO-VATC QC09BB05
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
WHO-VATC QC08CA02
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
NDF-RT N0000007556
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
LIVERTOX 402
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
NDF-RT N0000175421
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
NDF-RT N0000000069
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
WHO-ATC C09BB05
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
Code System Code Type Description
CAS
72509-76-3
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY
MERCK INDEX
M5257
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY Merck Index
WIKIPEDIA
FELODIPINE
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY
DRUG BANK
DB01023
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY
DRUG CENTRAL
1142
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY
RXCUI
4316
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY RxNorm
MESH
D015736
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY
PUBCHEM
3333
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY
EPA CompTox
72509-76-3
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY
EVMPD
SUB11963MIG
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY
LACTMED
Felodipine
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY
INN
4877
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY
FDA UNII
OL961R6O2C
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY
IUPHAR
4190
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY
USP_CATALOG
1269389
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY USP-RS
ChEMBL
CHEMBL1480
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY
NCI_THESAURUS
C29046
Created by admin on Fri Jun 25 21:02:58 UTC 2021 , Edited by admin on Fri Jun 25 21:02:58 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
ENANTIOMER -> RACEMATE
ENANTIOMER -> RACEMATE
TARGET -> INHIBITOR
Related Record Type Details
METABOLITE -> PARENT
MAJOR
PLASMA
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC