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| Targets |
The primary target of Niludipine is the L-type calcium channel (also known as the dihydropyridine receptor) in vascular smooth muscle and cardiac tissue. It acts as a calcium channel blocker (CCB) by binding to the alpha-1 subunit of the L-type calcium channel, specifically at the dihydropyridine binding site. This binding inhibits the influx of extracellular calcium ions through the channel, thereby reducing intracellular calcium concentrations. In vascular smooth muscle, this leads to relaxation and vasodilation, while in cardiac tissue, it results in negative inotropic (reduced contractility) and negative chronotropic (reduced heart rate) effects. The compound's vasodilatory action is particularly pronounced on coronary arteries, making it effective for treating angina pectoris. Niludipine's mechanism of action is similar to that of other dihydropyridine calcium channel blockers such as nifedipine, but its unique ester side chains confer distinct pharmacokinetic and tissue-selectivity properties.
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| ln Vitro |
In vitro, Niludipine has been shown to inhibit acetylcholine-induced contraction of isolated rabbit coronary arteries. It inhibits calcium influx through L-type calcium channels in various cell types, including vascular smooth muscle cells and cardiomyocytes. The compound has also been studied for its ability to perturb liposomal membranes prepared from platelet lipids, although its effect is minor compared to other calcium channel blockers such as verapamil and diltiazem. Niludipine inhibits the binding of calcium antagonist ligands to mitochondrial membranes, with an IC50 of 2.1 μM. The compound demonstrates potent vasorelaxant activity in isolated arterial preparations, consistent with its mechanism as a dihydropyridine calcium channel blocker. In vitro studies have also examined its effects on platelet aggregation, where it shows activity comparable to other DHP compounds.
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| ln Vivo |
In vivo, Niludipine is an orally active calcium channel blocker and vasodilator with antihypertensive effects. It has been shown to improve early fatal ventricular arrhythmias induced by acute myocardial ischemia in rats. The compound reduces left ventricular workload and has beneficial effects in models of coronary heart disease and myocardial ischemia. In animal models, niludipine demonstrates potent and long-lasting antihypertensive activity, with a broad range of efficacy for all types of angina. Studies comparing niludipine with other calcium channel blockers have shown that it has a minor perturbation effect on liposomal membranes, suggesting a favorable safety profile. The compound's vasodilatory action on coronary arteries makes it particularly useful for treating ischemic heart disease. In vivo experiments have also investigated its neuroprotective effects in models of neurotoxicity.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for Niludipine typically involve radioligand binding studies using cell membranes or tissue homogenates expressing L-type calcium channels. Competitive binding assays are performed using a radiolabeled dihydropyridine ligand, such as [3H]nitrendipine or [3H]nimodipine, to determine the compound's affinity for the calcium channel. The compound's ability to displace the radioligand is measured, and IC50 or Ki values are calculated from dose-response curves. Photoaffinity labeling studies using [3H]ludopamil have been employed to characterize niludipine binding to mitochondrial calcium antagonist receptors. These assays typically use purified mitochondrial membranes or tissue homogenates, and binding is assessed in the presence of ATP and other modulators. The compound's IC50 for displacement of radiolabeled ligands from mitochondrial binding sites is approximately 2.1 μM.
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| Cell Assay |
In vitro cellular assays for Niludipine are conducted using vascular smooth muscle cells, cardiomyocytes, or other cell types expressing L-type calcium channels. Cells are treated with varying concentrations of niludipine, and calcium influx is measured using fluorescent calcium indicators such as Fura-2 or Fluo-4. The compound's ability to inhibit calcium influx in response to depolarization or agonist stimulation is quantified. In isolated tissue preparations, such as rabbit coronary arteries, niludipine inhibits acetylcholine-induced contraction, providing a functional readout of calcium channel blockade. The compound's effects on platelet aggregation can be assessed in platelet-rich plasma using aggregometry. Membrane perturbation studies using liposomes prepared from platelet lipids provide information about the compound's interaction with lipid bilayers.
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| Animal Protocol |
In vivo animal studies for Niludipine are typically conducted in rat models of hypertension, myocardial ischemia, and arrhythmias. In the rat model of acute myocardial ischemia, niludipine is administered orally or intravenously, and its effects on ventricular arrhythmias, including ventricular tachycardia and fibrillization, are monitored using electrocardiography. The compound's antihypertensive effects are assessed in spontaneously hypertensive rats by measuring blood pressure before and after treatment. In models of angina, niludipine's ability to dilate coronary arteries and improve myocardial blood flow is evaluated. The compound has also been studied in models of neurotoxicity, where its neuroprotective effects are assessed. Survival rates and reduction in arrhythmia severity are key endpoints in these studies.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Niludipine indicate that it is an orally active compound with good bioavailability. As a dihydropyridine calcium channel blocker, it is highly lipophilic and extensively protein-bound in plasma. The compound undergoes significant first-pass metabolism in the liver, and its pharmacokinetic profile is characterized by a relatively short half-life. Niludipine is metabolized primarily by cytochrome P450 enzymes, particularly the CYP3A4 isoform. The compound's bis(2-propoxyethyl) ester structure distinguishes it from other DHP compounds and contributes to its unique pharmacokinetic properties. The compound is available as a solid for research purposes and should be stored under appropriate conditions to maintain stability. Its solubility in organic solvents facilitates formulation for in vivo administration.
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| Toxicity/Toxicokinetics |
Toxicological information for Niludipine is derived from preclinical studies in animal models. As a calcium channel blocker, potential on-target effects include hypotension, reflex tachycardia, and peripheral edema, which are well-documented class effects of dihydropyridine compounds. The compound's minor perturbation effect on liposomal membranes suggests a favorable safety profile compared to other calcium channel blockers. In animal studies, niludipine has been shown to be well-tolerated at therapeutic doses, with no significant adverse effects reported. However, comprehensive toxicology studies, including acute and repeated-dose toxicity in rodent and non-rodent species, genotoxicity assessments, and cardiovascular safety evaluations, would be required for clinical development. The compound's effects on cardiac function, vascular tone, and electrolyte balance would be particularly important to monitor.
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| Additional Infomation |
Niludipine is a calcium channel blocker.
Niludipine is a dihydropyridine class L-type calcium channel blocker and a bis(2-propoxyethyl) ester analog of nifedipine. It is also known as Bay a7168, niludipina, and niludipinum. The compound functions as a vasodilator with pronounced action on coronary arteries and is used for the treatment of both ischemic heart disease and essential hypertension. Niludipine was first synthesized in 1984 by Nippon Shinyaku Co. Ltd. It has a broad range of efficacy for all types of angina and is also a safe anti-angina Ca2+ antagonist. The compound has been studied for its ability to improve early fatal ventricular arrhythmias induced by acute myocardial ischemia in rats. Niludipine is not approved for clinical use in many jurisdictions and is available from research chemical suppliers for preclinical studies. |
| Molecular Formula |
C25H34N2O8
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|---|---|
| Molecular Weight |
490.553
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| Exact Mass |
490.232
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| CAS # |
22609-73-0
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| PubChem CID |
89767
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.176 g/cm3
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| Boiling Point |
597.4ºC
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| Flash Point |
315.1ºC
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| Vapour Pressure |
3.1E-14mmHg at 25°C
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| Index of Refraction |
1.528
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| LogP |
4.621
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
35
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| Complexity |
754
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCOCCOC(C1=C(C)NC(C)=C(C(OCCOCCC)=O)C1C1=CC=CC([N+]([O-])=O)=C1)=O
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| InChi Key |
VZWXXKDFACOXNT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H34N2O8/c1-5-10-32-12-14-34-24(28)21-17(3)26-18(4)22(25(29)35-15-13-33-11-6-2)23(21)19-8-7-9-20(16-19)27(30)31/h7-9,16,23,26H,5-6,10-15H2,1-4H3
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| Chemical Name |
bis(2-propoxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
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| Synonyms |
BAY-a 7168 BAY-a7168Niludipinum Niludipina
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0385 mL | 10.1926 mL | 20.3853 mL | |
| 5 mM | 0.4077 mL | 2.0385 mL | 4.0771 mL | |
| 10 mM | 0.2039 mL | 1.0193 mL | 2.0385 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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