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

SMILES

CCOC(=O)C1=C(C)NC(C)=C(C1C2=CC=CC(Cl)=C2Cl)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	MOL RATIO 1 MOL RATIO (average)

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

Description

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 53	Antagonist 2,849	0.17 µM [IC50]
Cholangiocarcinoma Mz-ChA-1 cells 1	Inhibitor 8,504	26.0 µM [IC50]
Cytochrome P450 2C8 18	Inhibitor 8,504	0.726 µM [IC50]
Voltage-gated L-type calcium channel alpha-1C subunit 44	Inhibitor 8,504
Voltage-gated calcium channel alpha2/delta subunit 1 19	Inhibitor 8,504
Voltage-dependent L-type calcium channel subunit beta-2 1	Inhibitor 8,504
Voltage-gated L-type calcium channel alpha-1D subunit 2	Inhibitor 8,504
Voltage-gated L-type calcium channel alpha-1S subunit 1	Inhibitor 8,504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575	Primary		Approved 8,583	PLENDIL

C_max

Value	Dose	Analyte	Population
23.1 nM	10 mg 2 times / day steady-state, oral	FELODIPINE plasma	Homo sapiens
35.6 nM	10 mg 2 times / day steady-state, oral	DEHYDROFELODIPINE plasma	Homo sapiens
6.2 nM	5 mg 2 times / day steady-state, oral	FELODIPINE plasma	Homo sapiens
17.1 nM	5 mg 2 times / day steady-state, oral	FELODIPINE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
100.9 nM × h	10 mg 2 times / day steady-state, oral	FELODIPINE plasma	Homo sapiens
142 nM × h	10 mg 2 times / day steady-state, oral	DEHYDROFELODIPINE plasma	Homo sapiens
33.7 nM × h	5 mg 2 times / day steady-state, oral	FELODIPINE plasma	Homo sapiens
87.5 nM × h	5 mg 2 times / day steady-state, oral	FELODIPINE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
23.1 h	10 mg 2 times / day steady-state, oral	FELODIPINE plasma	Homo sapiens
14.1 h	5 mg 2 times / day steady-state, oral	FELODIPINE plasma	Homo sapiens
27.5 h	5 mg 2 times / day steady-state, oral	FELODIPINE plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
20 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 51.5 (39-68)	Disc. AE: Headache, Ankle edema...

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AEs

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AE	Significance	Dose	Population
Headache	18% Disc. AE	20 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 51.5 (39-68)
Nausea	2% Disc. AE	20 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 51.5 (39-68)
Palpitation	2% Disc. AE	20 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 51.5 (39-68)
Vertigo	2% Disc. AE	20 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 51.5 (39-68)
Ankle edema	6% Disc. AE	20 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 51.5 (39-68)

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,946

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1,057	P-gp 2,052 CYP1A2 1,197

Drug as perpetrator

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Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C8 1,117	inhibitor 4,027	yes [IC50 0.726 uM]

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Drug as victim

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Target	Modality	Activity	Clinical evidence
CYP1A2 1,197	substrate 4,014	yes
P-gp 2,052	substrate 4,014	yes
CYP3A4 1,946	substrate 4,014	yes	yes (co-administration study)

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Sourcing

Sourcing

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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
eMolecules	538533	https://www.emolecules.com/cgi-bin/more?vid=538533
MolPort	MolPort-002-801-136	https://www.molport.com/shop/molecule-link/MolPort-002-801-136

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PubMed

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Title	Date	PubMed
		252160156
Haemodynamic effects of single-dose felodipine in normal man.	1985	3987549
Effects of felodipine on resistance and capacitance vessels in patients with essential hypertension.	1985	3921338
Comparative trial of felodipine and nifedipine in refractory hypertension.	1985	3886357
Antihypertensive effect of felodipine or hydralazine when added to beta-blocker therapy.	1988 Jul	2459541

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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.