SMPDB

Pathway Description

Felodipine Metabolism Pathway

Homo sapiens

Drug Metabolism Pathway

Created: 2013-09-11

Last Updated: 2025-01-24

Felodipine is a medication used to treat hypertension (high blood pressure). Untreated hypertension can lead to a heart attack, heart disease or stroke. High sodium intake can contribute to hypertension. Felodipine works by blocking calcium channels in vascular smooth muscle cells, stabilizing these voltage-gated L-type calcium channels, which will stop calcium-dependent myocyte vasoconstriction. This widens the blood vessels, allowing for more blood to pass through, lowering blood pressure. When used to treat angina, felodipine acts through improving the amount of blood pumping to the heart. Hypertension is a very common condition in North America, and can be managed with medication, diet and a healthy lifestyle. This pathway depicts the pharmacological action of felodipine on arterial smooth muscle cells. Felodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. 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. .

References

Felodipine Pathway References

Plendil. (2009). e-CPS (online version of Compendium of Pharmaceuticals and Specialties). Retrieved August 13, 2009.

Striessnig, J. Ca 2+ channel blockers. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (2004) p. 201-207. Berlin, Germany: Springer.

Soldatov NM: Molecular diversity of L-type Ca2+ channel transcripts in human fibroblasts. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4628-32. doi: 10.1073/pnas.89.10.4628.

Pubmed: 1316612

Schultz D, Mikala G, Yatani A, Engle DB, Iles DE, Segers B, Sinke RJ, Weghuis DO, Klockner U, Wakamori M, et al.: Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6228-32. doi: 10.1073/pnas.90.13.6228.

Pubmed: 8392192

Soldatov NM: Genomic structure of human L-type Ca2+ channel. Genomics. 1994 Jul 1;22(1):77-87. doi: 10.1006/geno.1994.1347.

Pubmed: 7959794

Klugbauer N, Lacinova L, Marais E, Hobom M, Hofmann F: Molecular diversity of the calcium channel alpha2delta subunit. J Neurosci. 1999 Jan 15;19(2):684-91.

Pubmed: 9880589

Gao B, Sekido Y, Maximov A, Saad M, Forgacs E, Latif F, Wei MH, Lerman M, Lee JH, Perez-Reyes E, Bezprozvanny I, Minna JD: Functional properties of a new voltage-dependent calcium channel alpha(2)delta auxiliary subunit gene (CACNA2D2). J Biol Chem. 2000 Apr 21;275(16):12237-42. doi: 10.1074/jbc.275.16.12237.

Pubmed: 10766861

Hobom M, Dai S, Marais E, Lacinova L, Hofmann F, Klugbauer N: Neuronal distribution and functional characterization of the calcium channel alpha2delta-2 subunit. Eur J Neurosci. 2000 Apr;12(4):1217-26. doi: 10.1046/j.1460-9568.2000.01009.x.

Pubmed: 10762351

Powers PA, Liu S, Hogan K, Gregg RG: Skeletal muscle and brain isoforms of a beta-subunit of human voltage-dependent calcium channels are encoded by a single gene. J Biol Chem. 1992 Nov 15;267(32):22967-72.

Pubmed: 1385409

Williams ME, Feldman DH, McCue AF, Brenner R, Velicelebi G, Ellis SB, Harpold MM: Structure and functional expression of alpha 1, alpha 2, and beta subunits of a novel human neuronal calcium channel subtype. Neuron. 1992 Jan;8(1):71-84. doi: 10.1016/0896-6273(92)90109-q.

Pubmed: 1309651

Collin T, Wang JJ, Nargeot J, Schwartz A: Molecular cloning of three isoforms of the L-type voltage-dependent calcium channel beta subunit from normal human heart. Circ Res. 1993 Jun;72(6):1337-44. doi: 10.1161/01.res.72.6.1337.

Pubmed: 7916667

Highlighted elements will appear in red.

Highlight Compounds

Felodipine

Highlight Proteins

	Voltage-dependent calcium channel subunit alpha-2/delta-2
	Voltage-dependent L-type calcium channel subunit alpha-1C
	Voltage-dependent L-type calcium channel subunit beta-1

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Visualize Compound Data

Felodipine

Visualize Protein Data

		Voltage-dependent calcium channel subunit alpha-2/delta-2
		Voltage-dependent L-type calcium channel subunit alpha-1C
		Voltage-dependent L-type calcium channel subunit beta-1