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Pathway Description
Amlodipine Action Pathway
Homo sapiens
Drug Action Pathway
Amlodipine, trade name Norvasc, is a dihydropyridine calcium channel blocker (CCB) prescribed to treat hypertension and exertion-related angina. The drug acts directly on vascular smooth muscle to cause peripheral vasodilation. Amlodipine inhibits the influx of calcium ions into vascular smooth muscle and cardiac muscle to bind calmodulin. Inhibition of calcium bound calmodulin prevents activation of myosin light chain kinase and phosphorylation of the regulatory light chain subunit of myosin, this inhibits an integral part of muscle contractions. The net effect is decreased contractility of arterial smooth muscle and increased vasodilation resulting in a decrease in blood pressure. Amlodipine has arterial selectivity due to alternative splicing of the channel and has little effect on cardiac muscle.
References
Amlodipine Pathway References
Norvasc. (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.
Shirley M, McCormack PL: Perindopril/amlodipine (Prestalia((R))): a review in hypertension. Am J Cardiovasc Drugs. 2015 Oct;15(5):363-70. doi: 10.1007/s40256-015-0144-1.
Pubmed: 26341621
Khodadoustan S, Nasri Ashrafi I, Vanaja Satheesh K, Kumar C, Hs S, S C: Evaluation of the effect of time dependent dosing on pharmacokinetic and pharmacodynamics of amlodipine in normotensive and hypertensive human subjects. Clin Exp Hypertens. 2017;39(6):520-526. doi: 10.1080/10641963.2017.1281947. Epub 2017 Jun 9.
Pubmed: 28598202
Striated Muscle Contraction References
Cooke R: The sliding filament model: 1972-2004. J Gen Physiol. 2004 Jun;123(6):643-56. doi: 10.1085/jgp.200409089.
Pubmed: 15173218
Szent-Gyorgyi A: The mechanism of muscle contraction. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3343-4.
Pubmed: 4610574
Kuo IY, Ehrlich BE: Signaling in muscle contraction. Cold Spring Harb Perspect Biol. 2015 Feb 2;7(2):a006023. doi: 10.1101/cshperspect.a006023.
Pubmed: 25646377
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