Felodipine

• Catalog No.: S1885
• CAS Number: 72509-76-3
• M. F.: C18H19Cl2NO4
• M. W.: 384.25376
• Storage: -20°C

SYNONYMS

• IUPAC name: 3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• IUPAC Traditional name: felodipine
• Synonyms: Renedil; Feloday; Plendil

DATABASE IDS

• CAS Number: 72509-76-3

PROPERTIES

• Salt Data: Free Base
• Storage Condition: -20°C

DETAILS

Description (English)

Research Area

• Description: Cardiovascular Disease

Biological Activity

• Description: Felodipine (Plendil) is a selective L-type Ca^2+ channel blocker with IC50 of 0.15 nM.
• Targets: L-type Ca^2+ channel
• IC50: 0.15 nM ^[1]
• In Vitro: Felodipine significantly relaxes KCl-contracted porcine coronary segments by blocking the Ca^2+ channels, displaying ~50 times more potent than nifedipine (IC50 of ~8 nM) and ~430 times than verapamil (IC50 of ~65 nM). ^[1] Felodipine significantly induces the transcription and secretion of IL-6 and IL-8 with ED50 values of 5.8 nM and 5.3 nM in primary human VSMC and lung fibroblasts, respectively, while propranolol or furosemide fails to affect the expression of the two IL genes. ^[2] Felodipine blocks the muscarinic receptor-mediated (carbachol) Ca^2+-dependent contraction of guinea pig ileum longitudinal smooth muscle (GPILSM) with an IC50 of 1.45 nM. ^[3] Felodipine at low concentration of 0.1 μM is sufficient to increases NOx generation, Ca^2+-dependent NOS activity, and eNOS protein mass in rat endothelial cells. ^[4] Felodipine (10 μM) reduces nuclear translocation of p42/44 mitogen-activated protein kinase and Elk-1 activation stimulated by PDGF-BB, leading to the inhibition of human SMC proliferation. ^[5] Felodipine modestly blocks the Ca_v3.2 T-type Ca^2+-channel with an IC50 of 6.8 μM. ^[6]
• In 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. ^[7] 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. ^[8]
• Clinical Trials: A Phase I study to evaluate the pharmacokinetic interaction between Candesartan and Felodipine in a combination package compared to the separate intake of the reference brands Atacand and Splendil after a fasting period has been completed.
• Features: Unlike many other Ca^2+ channel blockers, Felodipine does not exhibit cardiac side effects due to its significant selectivity toward vascular smooth muscle relative to myocardial tissue.

Protocol

• Protocol: Kinase Assay ^[1]
• The effect of Felodipine on tension in coronary segments: The cylindrical coronary segments from porcine hearts are inverted and fixed horizontally between a stationary bottom pin and a top pin connected to the lever of a force-displacement transducer precalibrated with standard weights on a Grass model 5D polygraph. The cylindrical segments are bathed in 25 mL of PSS in a water jacketed tissue bath at 37 °C. The bath solution is bubbled continuously with a mixture of 95% O₂-5% CO₂. An initial resting tension of 10 g is set during a 2-hour equilibration period. After the equilibration, three to four successive contraction-relaxation cycles are induced with 35 mM KCl and subsequent washes with PSS until reproducible contractions are obtained. After the final response reached and maintained steady tension (16-25 g above resting tension), a cumulative dose-response curve for Felodipine is obtained. Additional aliquots of Felodipine are added only after the response to the previous dose has plateaued. The concentration of Felodipine that half-maximally relaxes the coronary from KCl-induced contraction (IC50) is determined from dose response curve.
• Protocol: Animal Study ^[7]
• Animal Models: Male Sprague-Dawley rats with approximately 5/6 renal ablation
• Formulation: Dissolved in DMSO, and diluted in saline
• Doses: 1 g/kg/day
• Administration: Orally

References

• References: [1] Johnson JD, et al. J Pharmacol Exp Ther, 1983, 226(2), 330-334.
• References: [2] Rödler S, et al. J Mol Cell Cardiol, 1995, 27(10), 2295-2302.
• References: [3] Yiu S, et al. J Med Chem, 1996, 39(23), 4576-4582.
• References: [4] Ding Y, et al. Hypertension, 1998, 32(4), 718-723.
• References: [5] Yang Z, et al. Cardiovasc Res, 2002, 53(1), 227-231.
• References: [6] Perez-Reyes E, et al. J Pharmacol Exp Ther, 2009, 328(2), 621-627.

REFERENCES

• Johnson JD, et al. J Pharmacol Exp Ther, 1983, 226(2), 330-334.
• Rödler S, et al. J Mol Cell Cardiol, 1995, 27(10), 2295-2302.
• Yiu S, et al. J Med Chem, 1996, 39(23), 4576-4582.
• Ding Y, et al. Hypertension, 1998, 32(4), 718-723.
• Yang Z, et al. Cardiovasc Res, 2002, 53(1), 227-231.
• Perez-Reyes E, et al. J Pharmacol Exp Ther, 2009, 328(2), 621-627.