Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Flunarizine Calcium Channel Artery Dilation Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-06-16
Last Updated: 2023-11-27
Flunarizine is a selective calcium-entry blocker used as migraine prophylaxis in patients with severe and frequent episodes who have not responded adequately to more common treatments. Flunarizine is a selective calcium entry blocker with calmodulin binding properties and histamine H1 blocking activity. It is effective in the prophylaxis of migraine, occlusive peripheral vascular disease, vertigo of central and peripheral origin, and as an adjuvant in the therapy of epilepsy. Flunarizine inhibits the influx of extracellular calcium through myocardial and vascular membrane pores by physically plugging the channel. The decrease in intracellular calcium inhibits the contractile processes of smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload. Some side effects of using flunarizine may include tiredness, weight gain, and low mood. It can be found under the brand name Sibelium.
References
Flunarizine Calcium Channel Artery Dilation Pathway References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Steinbach LS, Ominsky SH, Shpall S, Perkocha LA: MR imaging of spindle cell hemangioendothelioma. J Comput Assist Tomogr. 1991 Jan-Feb;15(1):155-7. doi: 10.1097/00004728-199101000-00027.
Pubmed: 1987188
Amery WK: Flunarizine, a calcium channel blocker: a new prophylactic drug in migraine. Headache. 1983 Mar;23(2):70-4. doi: 10.1111/j.1526-4610.1983.hed2302070.x.
Pubmed: 6343298
Kurabayashi M, Komuro I, Tsuchimochi H, Takaku F, Yazaki Y: Molecular cloning and characterization of human atrial and ventricular myosin alkali light chain cDNA clones. J Biol Chem. 1988 Sep 25;263(27):13930-6.
Pubmed: 3417683
Hoffmann E, Shi QW, Floroff M, Mickle DA, Wu TW, Olley PM, Jackowski G: Molecular cloning and complete nucleotide sequence of a human ventricular myosin light chain 1. Nucleic Acids Res. 1988 Mar 25;16(5):2353. doi: 10.1093/nar/16.5.2353.
Pubmed: 3357795
Fodor WL, Darras B, Seharaseyon J, Falkenthal S, Francke U, Vanin EF: Human ventricular/slow twitch myosin alkali light chain gene characterization, sequence, and chromosomal location. J Biol Chem. 1989 Feb 5;264(4):2143-9.
Pubmed: 2789520
Lazar V, Garcia JG: A single human myosin light chain kinase gene (MLCK; MYLK). Genomics. 1999 Apr 15;57(2):256-67.
Pubmed: 10198165
Potier MC, Chelot E, Pekarsky Y, Gardiner K, Rossier J, Turnell WG: The human myosin light chain kinase (MLCK) from hippocampus: cloning, sequencing, expression, and localization to 3qcen-q21. Genomics. 1995 Oct 10;29(3):562-70. doi: 10.1006/geno.1995.9965.
Pubmed: 8575746
Garcia JG, Lazar V, Gilbert-McClain LI, Gallagher PJ, Verin AD: Myosin light chain kinase in endothelium: molecular cloning and regulation. Am J Respir Cell Mol Biol. 1997 May;16(5):489-94. doi: 10.1165/ajrcmb.16.5.9160829.
Pubmed: 9160829
Wawrzynczak EJ, Perham RN: Isolation and nucleotide sequence of a cDNA encoding human calmodulin. Biochem Int. 1984 Aug;9(2):177-85.
Pubmed: 6385987
Rhyner JA, Ottiger M, Wicki R, Greenwood TM, Strehler EE: Structure of the human CALM1 calmodulin gene and identification of two CALM1-related pseudogenes CALM1P1 and CALM1P2. Eur J Biochem. 1994 Oct 1;225(1):71-82. doi: 10.1111/j.1432-1033.1994.00071.x.
Pubmed: 7925473
Heilig R, Eckenberg R, Petit JL, Fonknechten N, Da Silva C, Cattolico L, Levy M, Barbe V, de Berardinis V, Ureta-Vidal A, Pelletier E, Vico V, Anthouard V, Rowen L, Madan A, Qin S, Sun H, Du H, Pepin K, Artiguenave F, Robert C, Cruaud C, Bruls T, Jaillon O, Friedlander L, Samson G, Brottier P, Cure S, Segurens B, Aniere F, Samain S, Crespeau H, Abbasi N, Aiach N, Boscus D, Dickhoff R, Dors M, Dubois I, Friedman C, Gouyvenoux M, James R, Madan A, Mairey-Estrada B, Mangenot S, Martins N, Menard M, Oztas S, Ratcliffe A, Shaffer T, Trask B, Vacherie B, Bellemere C, Belser C, Besnard-Gonnet M, Bartol-Mavel D, Boutard M, Briez-Silla S, Combette S, Dufosse-Laurent V, Ferron C, Lechaplais C, Louesse C, Muselet D, Magdelenat G, Pateau E, Petit E, Sirvain-Trukniewicz P, Trybou A, Vega-Czarny N, Bataille E, Bluet E, Bordelais I, Dubois M, Dumont C, Guerin T, Haffray S, Hammadi R, Muanga J, Pellouin V, Robert D, Wunderle E, Gauguet G, Roy A, Sainte-Marthe L, Verdier J, Verdier-Discala C, Hillier L, Fulton L, McPherson J, Matsuda F, Wilson R, Scarpelli C, Gyapay G, Wincker P, Saurin W, Quetier F, Waterston R, Hood L, Weissenbach J: The DNA sequence and analysis of human chromosome 14. Nature. 2003 Feb 6;421(6923):601-7. doi: 10.1038/nature01348. Epub 2003 Jan 1.
Pubmed: 12508121
Maldonado F, Hanks SK: A cDNA clone encoding human cAMP-dependent protein kinase catalytic subunit C alpha. Nucleic Acids Res. 1988 Aug 25;16(16):8189-90. doi: 10.1093/nar/16.16.8189.
Pubmed: 2843813
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Beebe SJ, Oyen O, Sandberg M, Froysa A, Hansson V, Jahnsen T: Molecular cloning of a tissue-specific protein kinase (C gamma) from human testis--representing a third isoform for the catalytic subunit of cAMP-dependent protein kinase. Mol Endocrinol. 1990 Mar;4(3):465-75. doi: 10.1210/mend-4-3-465.
Pubmed: 2342480
Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. doi: 10.1186/1471-2164-8-399.
Pubmed: 17974005
Groussin L, Jullian E, Perlemoine K, Louvel A, Leheup B, Luton JP, Bertagna X, Bertherat J: Mutations of the PRKAR1A gene in Cushing's syndrome due to sporadic primary pigmented nodular adrenocortical disease. J Clin Endocrinol Metab. 2002 Sep;87(9):4324-9. doi: 10.1210/jc.2002-020592.
Pubmed: 12213893
Sandberg M, Tasken K, Oyen O, Hansson V, Jahnsen T: Molecular cloning, cDNA structure and deduced amino acid sequence for a type I regulatory subunit of cAMP-dependent protein kinase from human testis. Biochem Biophys Res Commun. 1987 Dec 31;149(3):939-45. doi: 10.1016/0006-291x(87)90499-2.
Pubmed: 3426618
Sandberg M, Skalhegg B, Jahnsen T: The two mRNA forms for the type I alpha regulatory subunit of cAMP-dependent protein kinase from human testis are due to the use of different polyadenylation site signals. Biochem Biophys Res Commun. 1990 Feb 28;167(1):323-30. doi: 10.1016/0006-291x(90)91768-n.
Pubmed: 2310396
Manchev VT, Hilpert M, Berrou E, Elaib Z, Aouba A, Boukour S, Souquere S, Pierron G, Rameau P, Andrews R, Lanza F, Bobe R, Vainchenker W, Rosa JP, Bryckaert M, Debili N, Favier R, Raslova H: A new form of macrothrombocytopenia induced by a germ-line mutation in the PRKACG gene. Blood. 2014 Oct 16;124(16):2554-63. doi: 10.1182/blood-2014-01-551820. Epub 2014 Jul 24.
Pubmed: 25061177
Reinton N, Haugen TB, Orstavik S, Skalhegg BS, Hansson V, Jahnsen T, Tasken K: The gene encoding the C gamma catalytic subunit of cAMP-dependent protein kinase is a transcribed retroposon. Genomics. 1998 Apr 15;49(2):290-7. doi: 10.1006/geno.1998.5240.