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Felodipine (CGH869)

Alias: CGH-869; Perfudal, Plendil, Renedil,Felodipine,CGH 869;Felobeta, CGH869;Agon, Felo-Puren,Felocor, Felodipin,Felodur Felogamma, Fensel, Flodil, Modip, Munobal,
Cat No.:V0619 Purity: ≥98%
Felodipine (formerly also known as CGH-869; trade names Plendil, Renedil etc.
Felodipine (CGH869)
Felodipine (CGH869) Chemical Structure CAS No.: 72509-76-3
Product category: Calcium Channel
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
50mg
100mg
250mg
500mg
1g
5g
Other Sizes

Other Forms of Felodipine (CGH869):

  • Felodipine-d3 (felodipine d3)
  • Felodipine-d5
Official Supplier of:
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Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Felodipine (formerly also known as CGH-869; trade names Plendil, Renedil etc.), a marketed anti-hypertensive drug, is a potent, selective and long-acting L-type Ca2+ channel blocker (CCB) of the 1,4-dihydropyridine (DHP) class with an IC50 of 0.15 nM. It was approved to treat high blood pressure in 1988. Felodipine is described to inhibit cytokine-induced NO and superoxide production as well as cytokine-induced NO synthase (NOS) mRNA induction, and is suggested to act as a scavenger of superoxide and not an inhibitor of inducible NOS induction. This indicates that Felodipine further protects the vasculature against endogenous free radical generation during inflammatory responses.

Biological Activity I Assay Protocols (From Reference)
ln Vitro
The most efficient medication for relaxing pig coronary arteries is felodipine, a dihydropyridine calcium antagonist (IC50=0.15 nM) [1]. The L-type calcium channel blocker felodipine promotes autophagy and gets rid of a number of proteins linked to neurological diseases that are prone to aggregation [2]. With an IC50 of 1.45 nM, felodipine inhibits the contraction of guinea pig ileal longitudinal smooth muscle (GPILSM) mediated by muscarinic receptors (carbachol) in a Ca2+-dependent manner [3].
ln Vivo
Oral administration of Felodipine significantly reduces the average blood pressure (BP) in rats with 5/6 renal ablation, but causes additional impairment of the already impaired renal autoregulation. Administration of Felodipine significantly reduces systolic blood pressure (SBP), serum insulin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by blocking NF-κB activation, and decreases macrophages in the aortic wall, leading to the modulation of vascular inflammatory response.
Animal Protocol
Oral
Rats
ADME/Pharmacokinetics
Absorption, Distribution and Excretion
Is completely absorbed from the gastrointestinal tract; however, extensive first-pass metabolism through the portal circulation results in a low systemic availability of 15%. Bioavailability is unaffected by food.
Although higher concentrations of the metabolites are present in the plasma due to decreased urinary excretion, these are inactive. Animal studies have demonstrated that felodipine crosses the blood-brain barrier and the placenta.
10 L/kg
0.8 L/min [Young healthy subjects]
Metabolism / Metabolites
Hepatic metabolism primarily via cytochrome P450 3A4. Six metabolites with no appreciable vasodilatory effects have been identified.
Biological Half-Life
17.5-31.5 hours in hypertensive patients; 19.1-35.9 hours in elderly hypertensive patients; 8.5-19.7 in healthy volunteers.
Toxicity/Toxicokinetics
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because no information is available on the use of felodipine during breastfeeding, an alternate drug may be preferred.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
Protein Binding
99%, primarily to the albumin fraction.
References

[1]. Calcium and calmodulin antagonists binding to calmodulin and relaxation of coronary segments. J Pharmacol Exp Ther. 1983;226(2):330-334.

[2]. Felodipine induces autophagy in mouse brains with pharmacokinetics amenable to repurposing [published correction appears in Nat Commun. 2019 Jun 4;10(1):2530]. Nat Commun. 2019;10(1):1817. Published 2019 Apr 18.

[3]. Yiu, S. and E.E. Knaus, Synthesis, biological evaluation, calcium channel antagonist activity, and anticonvulsant activity of felodipine coupled to a dihydropyridine-pyridinium salt redox chemical delivery system. J Med Chem, 1996. 39(23): p. 4576-82.

Additional Infomation
Felodipine is the mixed (methyl, ethyl) diester of 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid. A calcium-channel blocker, it lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels. It is used in the management of hypertension and angina pectoris. It has a role as a calcium channel blocker, an antihypertensive agent, a vasodilator agent and an anti-arrhythmia drug. It is a dihydropyridine, a dichlorobenzene, an ethyl ester and a methyl ester.
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.
Felodipine is a Dihydropyridine Calcium Channel Blocker. The mechanism of action of felodipine is as a Calcium Channel Antagonist.
Felodipine is a second generation calcium channel blocker and commonly used antihypertensive agent. Felodipine therapy has been associated with a low rate of serum enzyme elevations, but has not been convincingly linked to instances of clinically apparent, acute liver injury.
Felodipine is a dihydropyridine calcium channel blocking agent. Felodipine inhibits the influx of extracellular calcium ions into myocardial and vascular smooth muscle cells, causing dilatation of the main coronary and systemic arteries and decreasing myocardial contractility. This agent also inhibits the drug efflux pump P-glycoprotein which is overexpressed in some multi-drug resistant tumors and may improve the efficacy of some antineoplastic agents. (NCI04)
A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels.
See also: Enalapril maleate; felodipine (component of).
Drug Indication
For the treatment of mild to moderate essential hypertension.
FDA Label
Mechanism of Action
Felodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through voltage-gated L-type calcium channels. It reversibly competes against nitrendipine and other DHP CCBs for DHP binding sites in vascular smooth muscle and cultured rabbit atrial cells. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of felodipine result in an overall decrease in blood pressure. Felodipine may be used to treat mild to moderate essential hypertension.
Pharmacodynamics
Felodipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction; however, some studies have shown that felodipine also binds to and inhibits T-type calcium channels. T-type calcium channels are most commonly found on neurons, cells with pacemaker activity and on osteocytes. The pharmacologic significance of T-type calcium channel blockade is unknown. Felodipine also binds to calmodulin and inhibits calmodulin-dependent calcium release from the sarcoplasmic reticulum. The effect of this interaction appears to be minor. Another study demonstrated that felodipine attenuates the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) by binding to the PDE-1B1 and PDE-1A2 enzyme subunits. CaMPDE is one of the key enzymes involved in cyclic nucleotides and calcium second messenger systems. Felodipine also acts as an antagonist to the mineralcorticoid receptor by competing with aldosterone for binding and blocking aldosterone-induced coactivator recruitment of the mineralcorticoid receptor. Felodipine is able to bind to skeletal and cardiac muscle isoforms of troponin C, one of the key regulatory proteins in muscle contraction. Though felodipine exhibits binding to many endogenous molecules, its vasodilatory effects are still thought to be brought about primarily through inhibition of voltage-gated L-type calcium channels. Similar to other DHP CCBs, felodipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives felodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, felodipine has little effect on cardiac myocytes and conduction cells.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C18H19CL2NO4
Molecular Weight
384.25
Exact Mass
383.069
CAS #
72509-76-3
Related CAS #
Felodipine-d3;1219795-30-8;Felodipine-d5;1242281-38-4
PubChem CID
3333
Appearance
Light yellow to yellow solid powder
Density
1.3±0.1 g/cm3
Boiling Point
471.5±45.0 °C at 760 mmHg
Melting Point
142-145°C
Flash Point
239.0±28.7 °C
Vapour Pressure
0.0±1.2 mmHg at 25°C
Index of Refraction
1.550
LogP
4.83
Hydrogen Bond Donor Count
1
Hydrogen Bond Acceptor Count
5
Rotatable Bond Count
6
Heavy Atom Count
25
Complexity
614
Defined Atom Stereocenter Count
0
InChi Key
RZTAMFZIAATZDJ-UHFFFAOYSA-N
InChi Code
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
Chemical Name
(RS)-3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
Synonyms
CGH-869; Perfudal, Plendil, Renedil,Felodipine,CGH 869;Felobeta, CGH869;Agon, Felo-Puren,Felocor, Felodipin,Felodur Felogamma, Fensel, Flodil, Modip, Munobal,
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO:77 mg/mL (200.4 mM)
Water:<1 mg/mL
Ethanol:77 mg/mL (200.4 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (6.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.6025 mL 13.0124 mL 26.0247 mL
5 mM 0.5205 mL 2.6025 mL 5.2049 mL
10 mM 0.2602 mL 1.3012 mL 2.6025 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05614037 Active, not recruiting Drug: Felodipine sustained
release tablets (trade name: plendil®)
Hypertension Overseas Pharmaceuticals, Ltd. October 28, 2022 Phase 1
NCT01238705 Unknown Drug: Felodipine add Irbesartan Hypertension
Sexual Dysfunction
LanZhou University April 2008 Phase 4
NCT00742066 Unknown Drug: Felodipine
Drug: Irbesartan
Hypertension
Insulin Resistance
Maastricht University
Medical Center
March 2008 Not Applicable
NCT05258448 Recruiting Other: Chemoradiotherapy Cardiac Toxicity
Lung Cancer Stage III
Odense University Hospital August 2015
NCT05788159 Not yet recruiting Drug: Lacosamide Tablets Epilepsy Overseas Pharmaceuticals, Ltd. April 1, 2023 Phase 1
Biological Data
  • Screening of L-type calcium channel blockers in primary neurons and zebrafish. Nat Commun. 2019;10(1):1817. Published 2019 Apr 18.
  • Felodipine in vivo dose-response experiments.Nat Commun. 2019;10(1):1817. Published 2019 Apr 18.
  • Efficacy study of felodipine in N171-82Q (B6HD) mice. Nat Commun. 2019;10(1):1817. Published 2019 Apr 18.
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