| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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| 1g |
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Purity: ≥98%
Nicorandil (formerly RP46417; SG-75; SG75; RP-46417; Dancor and Adancor) is a potassium channel activator that has been approved as a vasodilatory drug to treat angina. It stimulates guanylate cyclase to increase formation of cyclic GMP (cGMP). Nicorandil causes vasodilatation of arterioles and large coronary arteries. Nicorandal's nitrate-like properties produce venous vasodilation through stimulation of guanylate cyclase.
| Targets |
Potassium channel
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| ln Vitro |
Nicorandil (SG-75) activates ATP-sensitive K+ channels consisting of Kir6.2 and either sulfonylurea receptor (SUR) 2A or 2B[1]. Nicorandil is a vasodilatory medication used to treat angina. Nicorandil (SG-75) activates guanylate cyclase to promote synthesis of cyclic GMP (cGMP). cGMP stimulates protein kinase G (PKG) which phosphorylates and inhibits GTPase RhoA and reduces Rho-kinase activity. Reduced Rho-kinase activity promotes an increase in myosin phosphatase activity, lowering the calcium sensitivity of the smooth muscle. PKG also activates the sarcolemma calcium pump to remove activating calcium. PKG operates on K+ channels to increase K+ efflux and the resulting hyperpolarization inhibits voltage-gated calcium channels. Overall, this leads to relaxation of the smooth muscle and coronary vasodilation[2][3].
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| ln Vivo |
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| Enzyme Assay |
Nicorandil activates ATP-sensitive K+ channels composed of Kir6.2 and either sulfonylurea receptor (SUR) 2A or 2B. Although SUR2A and SUR2B differ only in their C-terminal 42 amino acids (C42) and possess identical drug receptors and nucleotide-binding domains (NBDs), nicorandil more potently activates SUR2B/Kir6.2 than SUR2A/Kir6.2 channels. Here, we analyzed the roles of NBDs in these channels' response to nicorandil with the inside-out configuration of the patch-clamp method. Binding and hydrolysis of nucleotides by NBDs were impaired by mutations in the Walker A motif of NBD1 (K708A) and NBD2 (K1349A) and in the Walker B motif of NBD2 (D1470N). Experiments were done with internal ATP (1 mM). In SUR2A/Kir6.2 channels, the K708A mutation abolished, and the K1349A but not D1470N mutation reduced the sensitivity to nicorandil. ADP (100 μM) significantly increased the wild-type channels' sensitivity to nicorandil, which was abolished by the K1349A or D1470N mutation. Thus, the SUR2A/Kir6.2 channels' response to nicorandil critically depends on ATP-NBD1 interaction and is facilitated by interactions of ATP or ADP with NBD2. In SUR2B/Kir6.2 channels, either the K708A or K1349A mutation partially suppressed the response to nicorandil, and double mutations abolished it. The D1470N mutation also significantly impaired the response. ADP did not sensitize the channels. Thus, NBD2 hydrolyzes ATP, and NBD1 and NBD2 equally contribute to the response by interacting with ATP and ADP, accounting for the higher nicorandil sensitivity of SUR2B/Kir6.2 than SUR2A/Kir6.2 channels in the presence of ATP alone. Thus, C42 modulates the interaction of both NBDs with intracellular nucleotides.[1]
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| Animal Protocol |
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
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. Steady-state plasma concentrations of nicorandil usually are reached within approximately 96-120 h after twice daily dosing (10 or 20mg). 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. 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%). Less than 2% of administered dose is excreted through the biliary system. After oral (and i.v.) administration of the drug, the apparent volume of distribution is approximately 1.0-1.4 L/kg body weight. The total body clearance is approximately 1.15 L/min. Metabolism / Metabolites Nicorandil undergoes extensive hepatic metabolism. 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. Biological Half-Life The elimination half life is approximately 1 hour. |
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| Toxicity/Toxicokinetics |
Protein Binding
Nicorandil is about 25% bound to human albumin and other plasma proteins. man TDLo oral 195 mg/kg/1Y-I GASTROINTESTINAL: OTHER CHANGES Lancet., 352(1598), 1998 [PMID:9843111] rat LD50 oral 1220 mg/kg Yakkyoku. Pharmacy., 35(1627), 1984 rat LD50 intraperitoneal 1100 mg/kg Yakkyoku. Pharmacy., 35(1627), 1984 rat LD50 subcutaneous 1200 mg/kg Yakkyoku. Pharmacy., 35(1627), 1984 rat LD50 intravenous 502 mg/kg SENSE ORGANS AND SPECIAL SENSES: LACRIMATION: EYE; BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX); LUNGS, THORAX, OR RESPIRATION: RESPIRATORY STIMULATION Yakuri to Chiryo. Pharmacology and Therapeutics., 19(2561), 1991 |
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| References |
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| Additional Infomation |
Pharmacodynamics
Nicorandil is a potassium channel opener with nitrovasodilator (NO donor) actions, making it both an arterial and a venous dilator. 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. 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. Open studies showed the effectiveness of nicorandil treatment on various types of angina pectoris. |
| Molecular Formula |
C8H9N3O4
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| Molecular Weight |
211.17
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| Exact Mass |
211.059
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| Elemental Analysis |
C, 45.50; H, 4.30; N, 19.90; O, 30.30
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| CAS # |
65141-46-0
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| Related CAS # |
Nicorandil-d4;1132681-23-2
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| PubChem CID |
47528
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
456.7±25.0 °C at 760 mmHg
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| Melting Point |
92ºC
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| Flash Point |
230.0±23.2 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.548
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| LogP |
0.72
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
15
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| Complexity |
228
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
LBHIOVVIQHSOQN-UHFFFAOYSA-N
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| InChi Code |
InChI=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)
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| Chemical Name |
2-(nicotinamido)ethyl nitrate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (11.84 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (11.84 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.7355 mL | 23.6776 mL | 47.3552 mL | |
| 5 mM | 0.9471 mL | 4.7355 mL | 9.4710 mL | |
| 10 mM | 0.4736 mL | 2.3678 mL | 4.7355 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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