| 词条 | Nicorandil |
| 释义 |
| Verifiedfields = changed | verifiedrevid = 417579163 | IUPAC_name = 2-[(pyridin-3-ylcarbonyl)amino]ethyl nitrate | image = Nicorandil.svg | tradename = | Drugs.com = {{drugs.com|international|nicorandil}} | pregnancy_AU = B3 | pregnancy_US = | pregnancy_category = | legal_AU = | legal_CA = | legal_UK = POM | legal_US = | legal_status = | routes_of_administration = Oral | bioavailability = 75 to 80% | protein_bound = 25% | metabolism = Hepatic | elimination_half-life = 1 hour | excretion = Renal (21%) | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 65141-46-0 | ATC_prefix = C01 | ATC_suffix = DX16 | PubChem = 47528 | IUPHAR_ligand = 2411 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 43240 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 260456HAM0 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D01810 | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 31905 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 284906 | C=8 | H=9 | N=3 | O=4 | molecular_weight = 211.175 g/mol | smiles = O=C(NCCO[N+]([O-])=O)c1cccnc1 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C8H9N3O4/c12-8(7-2-1-3-9-6-7)10-4-5-15-11(13)14/h1-3,6H,4-5H2,(H,10,12) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = LBHIOVVIQHSOQN-UHFFFAOYSA-N }} Nicorandil is a vasodilatory drug used to treat angina. Angina is chest pain that results from episodes of transient myocardial ischemia. This can be caused by diseases such as atherosclerosis, coronary artery disease and aortic stenosis. Angina commonly arises from vasospasm of the coronary arteries. There are multiple mechanisms causing the increased smooth muscle contraction involved in coronary vasospasm, including increased Rho-kinase activity. Increased levels of Rho-kinase inhibit myosin phosphatase activity, leading to increased calcium sensitivity and hypercontraction.[1] Rho-kinase also decreases nitric oxide synthase activity, which reduces nitric oxide concentrations.[2] Lower levels of nitric oxide are present in spastic coronary arteries.[3] L-type calcium channel expression increases in spastic vascular smooth muscle cells, which could result in excessive calcium influx, and hypercontraction.[4]It was patented in 1976 and approved for medical use in 1983.[5] Side effectsSide effects listed in the British National Formulary include flushing, palpitations, weakness and vomiting. More recently, perianal, ileal and peristomal ulceration has been reported as a side effect. Anal ulceration is now included in the British National Formulary as a reported side effect. Other side effects include severe toothache, and nasal congestion. Mechanism of actionNicorandil is an anti-angina medication that has the dual properties of a nitrate and ATP-sensitive {{chem|K|+}} channel agonist.[6] In humans, the nitrate action of nicorandil dilates the large coronary arteries at low plasma concentrations.[6] At high plasma concentrations nicorandil reduces coronary vascular resistance, which is associated with increased ATP-sensitive {{chem|K+}} channel (KATP) opening.[6] Nicorandil stimulates guanylate cyclase to increase formation of cyclic GMP (cGMP).[7] cGMP activates protein kinase G (PKG), which phosphorylates and inhibits GTPase RhoA and decreases Rho-kinase activity.[7] Reduced Rho-kinase activity permits an increase in myosin phosphatase activity, decreasing the calcium sensitivity of the smooth muscle.[7] PKG also activates the sarcolemma calcium pump to remove activating calcium.[8] PKG acts on {{chem|K|+}} channels to promote K+ efflux and the ensuing hyperpolarization inhibits voltage-gated calcium channels.[6] Overall, this leads to relaxation of the smooth muscle and coronary vasodilation. The effect of nicorandil as a vasodilator is mainly attributed to its nitrate property.[6] Yet, nicorandil is effective in cases where nitrates, such as nitroglycerine, are not effective.[6] Studies show that this is due to its KATP channel agonist action which causes pharmacological preconditioning and provides cardioprotective effects against ischemia.[6] Nicorandil activates KATP channels in the mitochondria of the myocardium, which appears to relay the cardioprotective effects, although the mechanism is still unclear.[9] NamesNicorandil is marketed under the trade names Ikorel (in the United Kingdom, Australia and most of Europe), Angedil (in Romania, Poland), Dancor (in Switzerland), Nikoran, PCA (in India), Aprior (in the Philippines), Nitorubin (in Japan), and Sigmart (in Japan, South Korea and Taiwan). Nicorandil is not available in the United States. See also
References1. ^{{cite journal|last=Kandabashi|first=T |author2=Shimokawa, H |author3=Miyata, K |author4=Kunihiro, I |author5=Kawano, Y |author6=Fukata, Y |author7=Higo, T |author8=Egashira, K |author9=Takahashi, S |author10=Kaibuchi, K |author11=Takeshita, A|title=Inhibition of myosin phosphatase by upregulated rho-kinase plays a key role for coronary artery spasm in a porcine model with interleukin-1beta.|journal=Circulation|date=Mar 21, 2000|volume=101|issue=11|pages=1319–23|pmid=10725293|doi=10.1161/01.cir.101.11.1319}} 2. ^{{cite journal|last=Takemoto|first=M|author2=Sun, J |author3=Hiroki, J |author4=Shimokawa, H |author5= Liao, JK |title=Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase.|journal=Circulation|date=Jul 2, 2002|volume=106|issue=1|pages=57–62|pmid=12093770 |doi=10.1161/01.cir.0000020682.73694.ab}} 3. ^{{cite journal|last=Kugiyama|first=K|author2=Yasue, H |author3=Okumura, K |author4=Ogawa, H |author5=Fujimoto, K |author6=Nakao, K |author7=Yoshimura, M |author8=Motoyama, T |author9=Inobe, Y |author10= Kawano, H |title=Nitric oxide activity is deficient in spasm arteries of patients with coronary spastic angina.|journal=Circulation|date=Aug 1, 1996|volume=94|issue=3|pages=266–71|pmid=8759065 |doi=10.1161/01.cir.94.3.266}} 4. ^{{cite journal|last=Kuga|first=T|author2=Shimokawa, H |author3=Hirakawa, Y |author4=Kadokami, Y |author5=Arai, Y |author6=Fukumoto, Y |author7=Kuwata, K |author8=Kozai, T |author9=Egashira, K |author10= Takeshita, A |title=Increased expression of L-type calcium channels in vascular smooth muscle cells at spastic site in a porcine model of coronary artery spasm.|journal=Journal of cardiovascular pharmacology|date=May 2000|volume=35|issue=5|pages=822–8|pmid=10813387 |doi=10.1097/00005344-200005000-00021}} 5. ^{{cite book |last1=Fischer |first1=Jnos |last2=Ganellin |first2=C. Robin |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=454 |url=https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA454 |language=en}} 6. ^1 2 3 4 5 6 {{cite journal|last=Nakae|first=I |author2=Matsumoto, T |author3=Horie, H |author4=Yokohama, H |author5=Omura, T |author6=Minai, K |author7=Matsui, T |author8=Nozawa, M |author9=Takahashi, M |author10=Sugimoto, Y |author11=Ito, M |author12=Izumi, M |author13=Nakamura, Y |author14=Mitsunami, K |author15=Kinoshita, M |title=Effects of intravenous nicorandil on coronary circulation in humans: plasma concentration and action mechanism.|journal=Journal of cardiovascular pharmacology|date=Jun 2000|volume=35|issue=6|pages=919–25|pmid=10836727|doi=10.1097/00005344-200006000-00014}} 7. ^1 2 {{cite journal|last=Sauzeau|first=V |author2=Le Jeune, H |author3=Cario-Toumaniantz, C |author4=Smolenski, A |author5=Lohmann, SM |author6=Bertoglio, J |author7=Chardin, P |author8=Pacaud, P |author9=Loirand, G |title=Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular smooth muscle.|journal=The Journal of Biological Chemistry|date=Jul 14, 2000|volume=275|issue=28|pages=21722–9|pmid=10783386|doi=10.1074/jbc.M000753200}} 8. ^{{cite journal |last=Vrolix|first=M|author2=Raeymaekers, L |author3=Wuytack, F |author4=Hofmann, F |author5= Casteels, R |title=Cyclic GMP-dependent protein kinase stimulates the plasmalemmal Ca2+ pump of smooth muscle via phosphorylation of phosphatidylinositol.|journal=The Biochemical Journal|date=Nov 1, 1988|volume=255|issue=3|pages=855–63|pmid=2850801 |pmc=1135320 |doi=10.1042/bj2550855}} 9. ^{{cite journal|last=Liu|first=Y|author2=Sato, T |author3=O'Rourke, B |author4= Marban, E |title=Mitochondrial ATP-dependent potassium channels: novel effectors of cardioprotection?|journal=Circulation|date=Jun 23, 1998|volume=97|issue=24|pages=2463–9|pmid=9641699 |doi=10.1161/01.cir.97.24.2463}} Further reading
6 : Antianginals|Vasodilators|Nitrate esters|Pyridines|Nicotinamides|Potassium channel openers |
| 随便看 |
开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。