FELODIPINE

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 Search

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

Molecular Formula	C18H19Cl2NO4
Molecular Weight	384.254
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.drugbank.ca/drugs/DB01023
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Mineralocorticoid receptor 52 Target ID: CHEMBL1994 Sources: http://www.drugbank.ca/drugs/DB01023	Antagonist 2737	0.17 µM [IC50]
Target ID: Cholangiocarcinoma Mz-ChA-1 cells Sources: https://www.ncbi.nlm.nih.gov/pubmed/21179572	Inhibitor 8146	26.0 µM [IC50]
Cytochrome P450 2C8 18 Target ID: CHEMBL3721 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15601807	Inhibitor 8146	0.726 µM [IC50]
Voltage-gated L-type calcium channel alpha-1C subunit 44 Target ID: CHEMBL1940 Sources: http://www.drugbank.ca/drugs/DB01023	Inhibitor 8146
Voltage-gated calcium channel alpha2/delta subunit 1 19 Target ID: CHEMBL1919 Sources: http://www.drugbank.ca/drugs/DB01023	Inhibitor 8146
Voltage-dependent L-type calcium channel subunit beta-2 1 Target ID: CHEMBL3317336 Sources: http://www.drugbank.ca/drugs/DB01023	Inhibitor 8146
Voltage-gated L-type calcium channel alpha-1D subunit 2 Target ID: CHEMBL4138 Sources: http://www.drugbank.ca/drugs/DB01023	Inhibitor 8146
Voltage-gated L-type calcium channel alpha-1S subunit 1 Target ID: CHEMBL3805 Sources: http://www.drugbank.ca/drugs/DB01023	Inhibitor 8146

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 546 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019834s025lbl.pdf	Primary		Approved 8307	PLENDIL Approved Use PLENDIL is indicated for the treatment of hypertension, to lower blood pressure. Launch Date 6.8031362E11

C_max

Value	Dose	Analyte	Population
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

Value	Dose	Analyte	Population
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

T_1/2

Value	Dose	Analyte	Population
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

Dose	Population	Adverse 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

AE	Significance	Dose	Population
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

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 869	P-gp 1491 CYP1A2 1013

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C8 923	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/15601807/	yes [IC50 0.726 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1013	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
P-gp 1491	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/23881850/	yes
CYP3A4 1670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019834s025lbl.pdf#page=6 Page: 6.0	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019834s025lbl.pdf#page=6 Page: 6.0

Sourcing

Vendor/Aggregator	ID	URL
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

Title	Date	PubMed
Baroreflex control of renin release in spontaneously hypertensive rats after administration of felodipine.	1987	3327681
Cardiovascular-risk reduction: initial diuretic therapy compared with calcium-antagonist (felodipine) therapy for primary hypertension.	1989 Sep 4	2671617
The influence of infusion rate on the hemodynamic effects of felodipine.	1990 Sep	2401128
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	1684748
Long-term effects of felodipine in patients with reduced renal function.	1992 May	1614060
General toxicity of the new calcium antagonist felodipine in dogs.	1993 Jul	8369003
A multicenter comparison of isradipine and felodipine in the treatment of mild-to-moderate hypertension. The Physician's Study Group.	1993 Mar	8466725
Efficacy and tolerability of extended-release felodipine and extended-release nifedipine in patients with mild-to-moderate essential hypertension.	1994 Jul-Aug	7982251
Isradipine. An update of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of mild to moderate hypertension.	1995 Apr	7789292
Global efficacy and tolerability of losartan, an angiotensin II subtype 1-receptor antagonist, in the treatment of hypertension.	1996	8913546
A comparison of nisoldipine coat-core and felodipine in the treatment of mild-to-moderate hypertension.	1998 Jun	9744143
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	9894374
Losartan: a review of its use, with special focus on elderly patients.	2000 Mar	10803861
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Optimal treatment of obesity-related hypertension: the Hypertension-Obesity-Sibutramine (HOS) study.	2007 Apr 17	17404163
Lercanidipine in the treatment of hypertension.	2007 Mar	17341540
A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle.	2010 Feb 23	20142494
Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11).	2013 Dec	24014644

Patents

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 16 16:18:05 UTC 2022` Edited by `admin` on `Fri Dec 16 16:18:05 UTC 2022`
Record UNII	OL961R6O2C
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FELODIPINE

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