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

Details

Stereochemistry RACEMIC
Molecular Formula C18H19Cl2NO4
Molecular Weight 384.254
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)=C(C1C2=C(Cl)C(Cl)=CC=C2)C(=O)OC

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

Description
Curator's Comment: Description was created based on several sources, including 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

CNS Penetrant
2554
Curator's Comment: Animal studies have demonstrated that felodipine crosses the blood-brain barrier and the placenta.

Originator

Approval Year

1991
113
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2778
 0.17 µM [IC50]
Cholangiocarcinoma Mz-ChA-1 cells
1
Target ID: Cholangiocarcinoma Mz-ChA-1 cells
Inhibitor
8297
 26.0 µM [IC50]
Inhibitor
8297
 0.726 µM [IC50]
Inhibitor
8297
Inhibitor
8297
Inhibitor
8297
Inhibitor
8297
Inhibitor
8297
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
PLENDIL

Approved Use

PLENDIL is indicated for the treatment of hypertension, to lower blood pressure.

Launch Date

1991
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
23.1 nM
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/2015166/
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3396260/
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3396260/
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/2015166/
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/2015166/
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3396260/
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3396260/
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/2015166/
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/2015166/
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3396260/
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3396260/
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:
https://pubmed.ncbi.nlm.nih.gov/2475701/
unhealthy, 51.5 (39-68)
n = 50
Health Status: unhealthy
Condition: hypertension
Age Group: 51.5 (39-68)
Sex: M+F
Population Size: 50
Sources:
https://pubmed.ncbi.nlm.nih.gov/2475701/
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:
https://pubmed.ncbi.nlm.nih.gov/2475701/
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:
https://pubmed.ncbi.nlm.nih.gov/2475701/
unhealthy, 51.5 (39-68)
n = 50
Health Status: unhealthy
Condition: hypertension
Age Group: 51.5 (39-68)
Sex: M+F
Population Size: 50
Sources:
https://pubmed.ncbi.nlm.nih.gov/2475701/
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:
https://pubmed.ncbi.nlm.nih.gov/2475701/
unhealthy, 51.5 (39-68)
n = 50
Health Status: unhealthy
Condition: hypertension
Age Group: 51.5 (39-68)
Sex: M+F
Population Size: 50
Sources:
https://pubmed.ncbi.nlm.nih.gov/2475701/
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:
https://pubmed.ncbi.nlm.nih.gov/2475701/
unhealthy, 51.5 (39-68)
n = 50
Health Status: unhealthy
Condition: hypertension
Age Group: 51.5 (39-68)
Sex: M+F
Population Size: 50
Sources:
https://pubmed.ncbi.nlm.nih.gov/2475701/
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:
https://pubmed.ncbi.nlm.nih.gov/2475701/
unhealthy, 51.5 (39-68)
n = 50
Health Status: unhealthy
Condition: hypertension
Age Group: 51.5 (39-68)
Sex: M+F
Population Size: 50
Sources:
https://pubmed.ncbi.nlm.nih.gov/2475701/
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:
https://pubmed.ncbi.nlm.nih.gov/2475701/
unhealthy, 51.5 (39-68)
n = 50
Health Status: unhealthy
Condition: hypertension
Age Group: 51.5 (39-68)
Sex: M+F
Population Size: 50
Sources:
https://pubmed.ncbi.nlm.nih.gov/2475701/
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:
https://pubmed.ncbi.nlm.nih.gov/2475701/
unhealthy, 51.5 (39-68)
n = 50
Health Status: unhealthy
Condition: hypertension
Age Group: 51.5 (39-68)
Sex: M+F
Population Size: 50
Sources:
https://pubmed.ncbi.nlm.nih.gov/2475701/
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP2C8
911
P-gp
1537

CYP1A2
1054
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2C8
965
 yes [IC50 0.726 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1054
 yes
P-gp
1537
 yes
CYP3A4
1737
 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: 6.0
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:585948
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:585948
ChemicalBook
CB4300661
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4300661
ChemicalBook
CB6411200
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6411200
MolPort
MolPort-002-801-136
https://www.molport.com/shop/molecule-link/MolPort-002-801-136
Selleck Chemicals
Felodipine(Plendil)
http://www.selleckchem.com/products/Felodipine(Plendil).html
eMolecules
538533
https://www.emolecules.com/cgi-bin/more?vid=538533
PubMed

PubMed

TitleDatePubMed
Effects of felodipine on resistance and capacitance vessels in patients with essential hypertension.
1985
Antihypertensive effect of felodipine combined with beta-blockade. A comparison between 2 and 3 daily dosages.
1985
Renal and cardiovascular effects of acute and chronic administration of felodipine to SHR.
1985 Jul 11
Monotherapy with felodipine, a new calcium antagonist, in mild and moderate hypertension.
1987
Antihypertensive effect of felodipine or hydralazine when added to beta-blocker therapy.
1988 Jul
Felodipine: a new dihydropyridine calcium-channel antagonist.
1991 Nov
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
Losartan potassium: a review of its pharmacology, clinical efficacy and tolerability in the management of hypertension.
1996 May
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
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
Stroke precipitated by moderate blood pressure reduction.
2000 Nov
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
Lercanidipine in the treatment of hypertension.
2007 Mar
Patents

Patents

06268377
3
JP2009526755A
447
JP2011529101A
66

Sample Use Guides

In Vivo Use Guide
Usual Adult Dose for Hypertension Initial dose: 5 mg orally once a day Maintenance dose: 2.5 to 10 mg orally once a day
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.
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
Felodipine [WHO-DD]
Common Name English
3,5-PYRIDINEDICARBOXYLIC ACID 4-(2,3-DICHLOROPHENYL)-1,4-DIHYDRO-2,6-DIMETHYL-, ETHYL METHYL ESTER, (±)-
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 [USP IMPURITY]
Common Name English
FELODIPINE [JAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C333
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
WHO-ATC C08CA02
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
WHO-VATC QC09BB05
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
WHO-VATC QC08CA02
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
NDF-RT N0000007556
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LIVERTOX NBK548294
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
NDF-RT N0000175421
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
NDF-RT N0000000069
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
WHO-ATC C09BB05
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
Code System Code Type Description
NSC
760343
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
PRIMARY
CAS
72509-76-3
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PRIMARY
MERCK INDEX
m5257
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PRIMARY Merck Index
WIKIPEDIA
FELODIPINE
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PRIMARY
DRUG BANK
DB01023
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PRIMARY
DRUG CENTRAL
1142
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PRIMARY
RXCUI
4316
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PRIMARY RxNorm
MESH
D015736
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PRIMARY
PUBCHEM
3333
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PRIMARY
EPA CompTox
DTXSID4023042
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PRIMARY
RS_ITEM_NUM
1269389
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PRIMARY
EVMPD
SUB11963MIG
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
PRIMARY
LACTMED
Felodipine
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
PRIMARY
INN
4877
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PRIMARY
DAILYMED
OL961R6O2C
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PRIMARY
CHEBI
585948
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
PRIMARY
USAN
X-2
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PRIMARY
FDA UNII
OL961R6O2C
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
PRIMARY
IUPHAR
4190
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PRIMARY
SMS_ID
100000089989
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PRIMARY
ChEMBL
CHEMBL1480
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
PRIMARY
NCI_THESAURUS
C29046
Created by admin on Fri Dec 15 15:08:32 GMT 2023 , Edited by admin on Fri Dec 15 15:08:32 GMT 2023
PRIMARY
ACTIVE MOIETY
Structure of FELODIPINE
METABOLITE (PARENT)
Structure of DEHYDROFELODIPINE
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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