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Systematic (IUPAC) name
2-[(pyridin-3-ylcarbonyl)amino]ethyl nitrate
Clinical data
AHFS/ International Drug Names
Legal status
  • UK: POM (Prescription only)
Routes of
Pharmacokinetic data
Bioavailability 75 to 80%
Protein binding 25%
Metabolism Hepatic
Biological half-life 1 hour
Excretion Renal (21%)
CAS Number 65141-46-0 YesY
ATC code C01DX16
PubChem CID: 47528
ChemSpider 43240 YesY
UNII 260456HAM0 YesY
KEGG D01810 YesY
Chemical data
Formula C8H9N3O4
Molecular mass 211.175 g/mol
 N (what is this?)  (verify)

Nicorandil is a vasodilatory drug used to treat angina. It 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.

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]

Nicorandil is an anti-angina medication that has the dual properties of a nitrate and K+ATP channel agonist.[5] In humans, the nitrate action of nicorandil dilates the large coronary arteries at low plasma concentrations.[5] At high plasma concentrations nicorandil reduces coronary vascular resistance, which is associated with increased K+ATP channel opening.[5]

Mechanism of action[edit]

Nitrate: Nicorandil stimulates guanylate cyclase to increase formation of cyclic GMP (cGMP).[6] cGMP activates protein kinase G (PKG) which phosphorylates and inhibits GTPase RhoA and decreases Rho-kinase activity.[6] Reduced Rho-kinase activity permits an increase in myosin phosphatase activity, decreasing the calcium sensitivity of the smooth muscle.

[6] PKG also activates the sarcolemma calcium pump to remove activating calcium.[7] PKG acts on K+ channels to promote K+ efflux and the ensuing hyperpolarization inhibits voltage-gated calcium channels.[5] 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.[5] Yet, nicorandil is effective in cases where nitrates, such as nitroglycerine, are not effective.[5] Studies show that this is due to its K+ATP channel agonist action which causes pharmacological preconditioning and provides cardioprotective effects against ischemia.[5] Nicorandil activates K+ATP channels in the mitochondria of the myocardium, which appears to relay the cardioprotective effects, although the mechanism is still unclear.[8]

Side effects[edit]

Side 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.

See also[edit]


  • Kukovetz WR, Holzmann S, Pöch G (1992). "Molecular mechanism of action of nicorandil". J. Cardiovasc. Pharmacol. 20 (Suppl 3): S1–7. PMID 1282168. 
  • Tripathi, K.D. Essentials of Medical Pharmacology. Ch. 37. p. 499. ISBN 8180611876. 
  • Dr.Hosny Mohaed, Brief ACSs.
  1. ^ Kandabashi, T; Shimokawa, H; Miyata, K; Kunihiro, I; Kawano, Y; Fukata, Y; Higo, T; Egashira, K; Takahashi, S; Kaibuchi, K; Takeshita, A (Mar 21, 2000). "Inhibition of myosin phosphatase by upregulated rho-kinase plays a key role for coronary artery spasm in a porcine model with interleukin-1beta.". Circulation 101 (11): 1319–23. doi:10.1161/01.cir.101.11.1319. PMID 10725293. 
  2. ^ Takemoto, M; Sun, J; Hiroki, J; Shimokawa, H; Liao, JK (Jul 2, 2002). "Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase.". Circulation 106 (1): 57–62. doi:10.1161/01.cir.0000020682.73694.ab. PMID 12093770. 
  3. ^ Kugiyama, K; Yasue, H; Okumura, K; Ogawa, H; Fujimoto, K; Nakao, K; Yoshimura, M; Motoyama, T; Inobe, Y; Kawano, H (Aug 1, 1996). "Nitric oxide activity is deficient in spasm arteries of patients with coronary spastic angina.". Circulation 94 (3): 266–71. doi:10.1161/01.cir.94.3.266. PMID 8759065. 
  4. ^ Kuga, T; Shimokawa, H; Hirakawa, Y; Kadokami, Y; Arai, Y; Fukumoto, Y; Kuwata, K; Kozai, T; Egashira, K; Takeshita, A (May 2000). "Increased expression of L-type calcium channels in vascular smooth muscle cells at spastic site in a porcine model of coronary artery spasm.". Journal of cardiovascular pharmacology 35 (5): 822–8. doi:10.1097/00005344-200005000-00021. PMID 10813387. 
  5. ^ a b c d e f g Nakae, I; Matsumoto, T; Horie, H; Yokohama, H; Omura, T; Minai, K; Matsui, T; Nozawa, M; Takahashi, M; Sugimoto, Y; Ito, M; Izumi, M; Nakamura, Y; Mitsunami, K; Kinoshita, M (Jun 2000). "Effects of intravenous nicorandil on coronary circulation in humans: plasma concentration and action mechanism.". Journal of cardiovascular pharmacology 35 (6): 919–25. doi:10.1097/00005344-200006000-00014. PMID 10836727. 
  6. ^ a b c Sauzeau, V; Le Jeune, H; Cario-Toumaniantz, C; Smolenski, A; Lohmann, SM; Bertoglio, J; Chardin, P; Pacaud, P; Loirand, G (Jul 14, 2000). "Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular smooth muscle.". The Journal of Biological Chemistry 275 (28): 21722–9. doi:10.1074/jbc.M000753200. PMID 10783386. 
  7. ^ Vrolix, M; Raeymaekers, L; Wuytack, F; Hofmann, F; Casteels, R (Nov 1, 1988). "Cyclic GMP-dependent protein kinase stimulates the plasmalemmal Ca2+ pump of smooth muscle via phosphorylation of phosphatidylinositol.". The Biochemical journal 255 (3): 855–63. PMC 1135320. PMID 2850801. 
  8. ^ Liu, Y; Sato, T; O'Rourke, B; Marban, E (Jun 23, 1998). "Mitochondrial ATP-dependent potassium channels: novel effectors of cardioprotection?". Circulation 97 (24): 2463–9. doi:10.1161/01.cir.97.24.2463. PMID 9641699.