Nicorandil is a vasodilatory drug that functions through potassium channels and intracellular cGMP concentrations commonly used to treat angina.

Generic Name
DrugBank Accession Number

Nicorandil is an orally efficacious vasodilatory drug and antianginal agent marketed in the UK, Australia, most of Europe, India, Philippines, Japan, South Korea, and Taiwan. It is not an approved drug by FDA. It is a niacinamide derivative that induces vasodilation of arterioles and large coronary arteries by activating potassium channels. It is often used for patients with angina who remain symptomatic despite optimal treatment with other antianginal drugs 11. Nicorandil is a dual-action potassium channel opener that relaxes vascular smooth muscle through membrane hyperpolarization via increased transmembrane potassium conductance and increased intracellular concentration of cyclic GMP. It is shown to dilate normal and stenotic coronary arteries and reduces both ventricular preload and afterload 10.

Small Molecule
Approved, Investigational
Average: 211.177
Monoisotopic: 211.059305782
Chemical Formula
  • 2-Nicotinamidoethyl nitrate
  • N-(2-Hydroxyethyl)nicotinamide nitrate
  • N-(2-Hydroxyethyl)nicotinamide nitrate (ester)
  • Nicorandil
  • Nicorandilum
External IDs
  • BRN 0481451
  • SG 75
  • SG-75



Indicated for the prevention and treatment of chronic stable angina pectoris and reduction in the risk of acute coronary syndromes.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAngina pectoris••••••••••••••••••
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Nicorandil is a potassium channel opener with nitrovasodilator (NO donor) actions, making it both an arterial and a venous dilator 11. It causes sustained dilation of both the arterial resistance and conductive vessels that increases coronary blood flow, however the effect of the drug on coronary arteries does not involve the coronary steal phenomenon 12. Activation of potassium channels lead to hyperpolarization of the smooth muscle cells, followed by arterial dilation and afterload reduction. Nicorandil is shown to increase pooling in the capacitance vessels with a decrease in preload through relaxing the venous vascular system. Overall, improved blood flow and reduced infarct size are achieved through reduction of end-diastolix pressure and decreased extravascular component of vascular resistance 12. Open studies showed the effectiveness of nicorandil treatment on various types of angina pectoris 8.

Mechanism of action

Nicorandil mediates its therapeutic efficacy via two main mechanisms. Nicorandil is an activator and opener of ATP-sensitive (ATP-dependent) potassium channels (KATP channels) that are composed of Kir6.x-type subunits and sulfonylurea receptor (SUR) subunits. Nicorandil binding sites are located in the sulfonylurea receptor 2 (SUR2) in the ATP-sensitive potassium channel 4, which are regulatory subunits of the channel that exhibit an ATPase activitiy 2. There are 2 types of SUR2 subunits (2A/2B) that have identical nucleotide binding domains (NBD), where SUR2A is more predominantly expressed in skeletal and cardiac myocytes and SUR2B in smooth muscle cells 2. Nicorandil more potently activates SUR2B/Kir6.2 than SUR2A/Kir6.2 channels to cause hyperpolarization. ATP-NBD1 interaction influences the channel signalling by nicorandil, and the response of the channel to nicorandil is also facilitated and heightened by the interaction of ATP or ADP with NBD2 3. Potentiated activity of ATP-sensitive channels have cardioprotective role by limiting the duration of action potentials and preventing intraceullar calcium overload 7. This attenuates cellular injury by preserving cellular energetics and ultimately cell survival 6. KATP channel-dependent membrane hyperpolarization can also lead to vasodilation via reduction in Ca2+ influx through the voltage-gated Ca2+ channels and regulation of intracellular Ca2+ mobilization in smooth muscle cells 6. Nicorandil contain a nitrate moiety in its structure, making it a good dilator of vascular smooth muscle like other nitroglycerin esters 5. Direct relaxation of venous vascular system arises from NO-donor mediated stimulation of guanylyl cyclase and increased levels of intracellular cyclic GMP (cGMP). Elevated levels of cGMP contributes to the total relaxing effect of nicorandil at higher concentrations of the drug 1.

AATP-binding cassette sub-family C member 9

Following oral administration, nicorandil is well absorbed from the gastrointestinal tract with the oral bioavailability of 75% with the maximum peak plasma concentration (Cmax) reached within 30-60 minutes. The mean Cmax is Cmax then is approximately 300 ng/ml 9. Steady-state plasma concentrations of nicorandil usually are reached within approximately 96-120 h after twice daily dosing (10 or 20mg) 12.

Volume of distribution

After oral (and i.v.) administration of the drug, the apparent volume of distribution is approximately 1.0-1.4 L/kg body weight 9.

Protein binding

Nicorandil is about 25% bound to human albumin and other plasma proteins 9.


Nicorandil undergoes extensive hepatic metabolism 12. The main biotransformation pathways of nicorandil are denitration, followed by subsequent nicotinamide metabolism. The main pharmacologically inactive denitrated metabolite 2-nicotinamidoethanol can be detected in the urine. The derivatives formed from the nicotinamide metabolism of denitrated products are nicotinuric acid, nicotinamide, N-methylnicotinamide and nicotinic acid 12.

Route of elimination

The main route of elimination is the kidney with more than 60% of the administered dose was eliminated in the urine 24 hours after dosing 12. Only approximately 1% of nicorandil is excreted unchanged in the urine, and the remaining compounds are mainly the denitrated metabolite (9%) and its derivatives (e.g. nicotinuric acid 6%, nicotinamide 1%, N-methylnicotinamide < 1% and nicotinic acid < 1%) 12. Less than 2% of administered dose is excreted through the biliary system 9.


The elimination half life is approximately 1 hour 9.


The total body clearance is approximately 1.15 L/min 9.

Adverse Effects
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Common adverse effects include lethargy, back pain, chest pain, infection, feeling of weakness. In the cardiovascular system, hypotension, increased heart rate in higher doses, palpitations, worsened angina pectoris and vasodilation/flush may be observed. Dyspepsia, nausea, and vomiting may occur as gastrointestinal disorders. Headaches may arise from vasodilation. Other common side effects include myalgia, bronchitis, dyspnoea, and respiratory disorder 12. Nicorandil does not affect fertility of male or female rats, and shows no potential in carcinogenic, mutagenic or genotoxic studies 12. Oral LD50 values in mouse, rat and dog are 626 mg/kg, 1220 mg/kg and 62.5 mg/kg, respectively MSDS.

Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
AbacavirAbacavir may decrease the excretion rate of Nicorandil which could result in a higher serum level.
AbaloparatideNicorandil may increase the hypotensive activities of Abaloparatide.
AcebutololNicorandil may increase the hypotensive activities of Acebutolol.
AceclofenacThe therapeutic efficacy of Nicorandil can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Nicorandil can be decreased when used in combination with Acemetacin.
Food Interactions
Not Available


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International/Other Brands
Adancor (Merck) / Angedil (Egis Pharmaceuticals) / Angicor (Sanofi-Aventis) / Aprior (OEP Phils) / Av-Cor (Strides Arcolab) / Corangi (Unimed & Unihealth) / Cordinik (PIQ-Farma) / Corflo (Wockhardt) / Dancor (Merck) / Ikorel (Sanofi) / Ikotril (Sanofi-aventis) / K-Cor (Macleods) / Nicodil (Genovate) / Nicoduce (AHPL) / Nicolan (G.L. Pharma) / Nicoline (Johnlee) / Nicor (Orion) / Nicoral (General Pharma) / Nicostar (Lupin) / Nidil (Shou Chan) / Nikoran (Torrent) / Nikoranmart (Towa Yakuhin) / Nirandil (Standard) / Randil (Adwia) / Sigmart (Chugai) / Silvinol (Nisshin Pharmaceutical) / Zynicor (Zydus)


ATC Codes
C01DX16 — Nicorandil
Drug Categories
Chemical TaxonomyProvided by Classyfire
This compound belongs to the class of organic compounds known as nicotinamides. These are heterocyclic aromatic compounds containing a pyridine ring substituted at position 3 by a carboxamide group.
Organic compounds
Super Class
Organoheterocyclic compounds
Pyridines and derivatives
Sub Class
Pyridinecarboxylic acids and derivatives
Direct Parent
Alternative Parents
Heteroaromatic compounds / Alkyl nitrates / Secondary carboxylic acid amides / Organic nitro compounds / Organic nitric acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organic zwitterions
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Alkyl nitrate / Allyl-type 1,3-dipolar organic compound / Aromatic heteromonocyclic compound / Azacycle / Carboxamide group / Carboxylic acid derivative / Heteroaromatic compound / Hydrocarbon derivative / Nicotinamide / Organic 1,3-dipolar compound
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyridinecarboxamide, nitrate ester (CHEBI:31905)
Affected organisms
Not Available

Chemical Identifiers

CAS number
InChI Key
2-[(pyridin-3-yl)formamido]ethyl nitrate


General References
  1. Kukovetz WR, Holzmann S, Poch G: Molecular mechanism of action of nicorandil. J Cardiovasc Pharmacol. 1992;20 Suppl 3:S1-7. [Article]
  2. Russ U, Lange U, Loffler-Walz C, Hambrock A, Quast U: Binding and effect of K ATP channel openers in the absence of Mg2+. Br J Pharmacol. 2003 May;139(2):368-80. [Article]
  3. Yamada M, Kurachi Y: The nucleotide-binding domains of sulfonylurea receptor 2A and 2B play different functional roles in nicorandil-induced activation of ATP-sensitive K+ channels. Mol Pharmacol. 2004 May;65(5):1198-207. [Article]
  4. Tamura Y, Tanabe K, Kitagawa W, Uchida S, Schreiner GF, Johnson RJ, Nakagawa T: Nicorandil, a K(atp) channel opener, alleviates chronic renal injury by targeting podocytes and macrophages. Am J Physiol Renal Physiol. 2012 Aug 1;303(3):F339-49. doi: 10.1152/ajprenal.00158.2012. Epub 2012 May 23. [Article]
  5. Fujiwara T, Angus JA: Analysis of relaxation and repolarization mechanisms of nicorandil in rat mesenteric artery. Br J Pharmacol. 1996 Dec;119(8):1549-56. [Article]
  6. Jahangir A, Terzic A: K(ATP) channel therapeutics at the bedside. J Mol Cell Cardiol. 2005 Jul;39(1):99-112. [Article]
  7. Kane GC, Liu XK, Yamada S, Olson TM, Terzic A: Cardiac KATP channels in health and disease. J Mol Cell Cardiol. 2005 Jun;38(6):937-43. Epub 2005 Apr 25. [Article]
  8. Frampton J, Buckley MM, Fitton A: Nicorandil. A review of its pharmacology and therapeutic efficacy in angina pectoris. Drugs. 1992 Oct;44(4):625-55. [Article]
  9. Frydman A: Pharmacokinetic profile of nicorandil in humans: an overview. J Cardiovasc Pharmacol. 1992;20 Suppl 3:S34-44. [Article]
  10. Goldschmidt M, Landzberg BR, Frishman WH: Nicorandil: a potassium channel opening drug for treatment of ischemic heart disease. J Clin Pharmacol. 1996 Jul;36(7):559-72. [Article]
  11. 21. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 261). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
  12. IKOREL (Nicorandil) Product Information [Link]
  13. UK Medicines and Healthcare products Regulatory Agency (MHRA): Nicorandil Tablets_Scientific Discussion [Link]
KEGG Compound
PubChem Compound
PubChem Substance
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Clinical Trials

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Not Available
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Dosage Forms
Not Available
Not Available


Experimental Properties
melting point (°C)92-93MSDS
water solubilityPartly miscibleMSDS
Predicted Properties
Water Solubility1.19 mg/mLALOGPS
pKa (Strongest Acidic)13.81Chemaxon
pKa (Strongest Basic)3.62Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area94.36 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity49.86 m3·mol-1Chemaxon
Polarizability19.34 Å3Chemaxon
Number of Rings1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available


Mass Spec (NIST)
Not Available
SpectrumSpectrum TypeSplash Key
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-004j-7920010011-f3cb0b77efee19ef8d89
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-0900000000-9439cd529fafd85e86db
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
DarkChem Lite v0.1.0
DeepCCS 1.0 (2019)
DarkChem Lite v0.1.0
DeepCCS 1.0 (2019)
DeepCCS 1.0 (2019)


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Pharmacological action
General Function
Transporter activity
Specific Function
Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with KCNJ11. KCNJ11 forms the channel pore while ABCC9 is required for activation and regul...
Gene Name
Uniprot ID
Uniprot Name
ATP-binding cassette sub-family C member 9
Molecular Weight
174221.7 Da
  1. Russ U, Lange U, Loffler-Walz C, Hambrock A, Quast U: Binding and effect of K ATP channel openers in the absence of Mg2+. Br J Pharmacol. 2003 May;139(2):368-80. [Article]

Drug created at October 22, 2015 00:43 / Updated at May 05, 2021 20:31