| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| 5g |
|
||
| 10g |
|
||
| Other Sizes |
|
Purity: ≥98%
Cilnidipine (formerly also known as FRC-8653; FRC8653; Atelec; Cinalong; Siscard) is a novel, potent and unique dual L-type and N-type calcium channel blocker (CCB) that was approved as an anti-hypertensive drug in 1995 for high blood pressure treatment. Cilnidipine lowers mean blood pressure and reduces the size of cerebral infarction in the rat model of focal brain ischemia. Cilnidipine has displayed renal and vascular protective effects and improved baroreflex sensitivity in patients with hypertension. It has also demonstrated neuroprotective effects in a rat focal brain ischemia model by removing free radicals and activating the phosphatidylinositol 3-kinase pathway.
| ln Vitro |
In neurons pretreated with omegaCgTx plus omegaAgTx, celidipine inhibits the L-type current with an IC50 of 100 nM[1]. Cilnidipine's IC50 with regard to the N-type current is 200 nM[1]. With an IC50 of 10 nM at 10 min, clinidipine dose- and time-dependently inhibits the contractions of rat aortic rings caused by depolarization and Ca2+[2]. When exposed to more than 200 μM of Cilnidipine, the viability of nPC12 cells decreases slightly, but does not change significantly up to 150 μM of the drug[3]. After two hours of treatment at 100 μM, cilnidipine increases the expression of p85aPI3K, p-Akt, p-GSK-3β, and heat shock transcription factor (HSTF-1), while cytosolic cytochrome c, activated caspase 3, and cleaved PARP levels decrease[3].
|
|---|---|
| ln Vivo |
In rat dorsal root ganglion neurons, cilnidipine has strong inhibitory effects on both L-type and N-type voltage-dependent Ca2+ channels[1]. The use of 10 mg/kg of cilnidipine and 10 mg/kg of nicodipine greatly reduces the behavioral abnormalities brought on by immobilization stress, restores deficit memories, and normalizes corticosterone levels[4]. Both nicodipine and clonidipine have similar positive effects on immobilized mice under stress[4]. In 2K1C renal hypertensive dogs, oral Cilnidipine (3 mg/kg) significantly reduces both systolic and diastolic blood pressure one hour after administration[5].
|
| Cell Assay |
Cell Viability Assay
Cell Types: Neuronally differentiated PC12 (nPC12) cells Tested Concentrations: 0, 1, 5, 10, 25, 50, 100, 150, and 200 μM Incubation Duration: Treated for 2 hrs (hours); cell viability was measured after 24 hrs (hours) Experimental Results: Cell viability was not affected by low concentrations up to 150 μM, but it was slightly diminished at 200 μM. Western Blot Analysis Cell Types: nPC12 cells Tested Concentrations: 100 μM Incubation Duration: 2 hrs (hours) Experimental Results: Increased the IRs of p58a PI3K, p-Akt, p-GSK-3β, and HSTF-1 and diminished the Immunoreactivities (IRs) of cytosolic cytochrome c, activated caspase 3 (17 kDa), and cleaved PARP (85 kDa). |
| Animal Protocol |
Animal/Disease Models: Swiss albino mice weighing 25±5 g[4]
Doses: 5 and 10 mg/kg Route of Administration: administered ip 30 min prior to immobilization stress Experimental Results: Cilnidipine (10 mg/kg, ip) and nimodipine (10 mg/kg, ip) 30 min prior to subjecting immobilization stress resulted in significant attenuation of immobilization stress-induced decrease in locomotor activity. Administration with Cilnidipine (5 mg /kg, ip) and Nimodipine (5 mg/kg, ip) did not show any significant effect on the stressed mice. Administration of Cilnidipine (10 mg/kg, ip) and Nimodipine (10 mg/kg, ip) in the non -stressed mice, and vehicle in the stressed mice did not modulate locomotor activity in a significant manner. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Cilnidipine presents a very rapid absorption with a maximum peaked concentration after 2 hours. Its distribution tends to be higher in the liver as well as in kidneys, plasma and other tissues. Cilnidipine does not present a high accumulation in the tissue after repeated oral administration. Cilnidipine is reported to present very low bioavailability determined to be approximately 13%. This low bioavailability is suggested to be due to its low aqueous solubility and high permeability. Hence, efforts have been made in order to find an innovative formulation that can significantly improve the bioavailability of this drug. One of these formulations corresponds to the generation of polymeric nanoparticles which enhance the bioavailability by 2.5-3-fold. Cilnidipine gets eliminated through the urine in a proportion of 20% of the administered dose and 80% is eliminated by the feces. Drugs on the group of dihydropyridines such as cilnidipine tend to have a large volume of distribution. Metabolism / Metabolites Cilnidipine is metabolized by both liver and kidney. It is rapidly metabolized by liver microsomes by a dehydrogenation process. The major enzymatic isoform involved in cilnidipine dehydrogenation of the dihydropyridine ring is CYP3A. Biological Half-Life The half-life of the hypotensive effect for cilnidipine is of about 20.4 min. |
| Toxicity/Toxicokinetics |
Protein Binding
Cilnidipine presents a very high protein binding that represents to even 98% of the administered dose. |
| References |
|
| Additional Infomation |
Cilnidipine is a diesterified 1,4-dihydropyridine-3,5-dicarboxylic acid. A calcium channel blocker, it is used as an antihypertensive. It has a role as a calcium channel blocker, an antihypertensive agent and a cardiovascular drug. It is a dihydropyridine, a 2-methoxyethyl ester and a C-nitro compound.
Cilnidipine is a dihydropyridine calcium antagonist. It was jointly developed by Fuji Viscera Pharmaceutical Company, Japan and Ajinomoto, Japan and approved in 1995. Compared with other calcium antagonists, cilnidipine can act on the N-type calcium channel that existing sympathetic nerve end besides acting on L-type calcium channel that similar to most of the calcium antagonists. This drug is approved in China, Japan, Korea, India, and several countries in the European Union. Drug Indication Cilnidipine is indicated for the management of hypertension for end-organ protection. It is reported to be useful in elderly patients and in those with diabetes and albuminuria. Cilnidipine has been increasingly used in patients with chronic kidney disease Hypertension is the term used to describe the presence of high blood pressure. The blood pressure is generated by the force of the blood pumped from the heart against the blood vessels. Thus hypertension is caused when there is too much pressure on the blood vessels and this effect can damage the blood vessel. Mechanism of Action Cilnidipine acts on the L-type calcium channels of blood vessels by blocking the incoming calcium and suppressing the contraction of blood vessels, thereby reducing blood pressure. Cilnidipine also works on the N-type calcium channel located at the end of the sympathetic nerve, inhibiting the emission of norepinephrine and suppressing the increase in stress blood pressure. Pharmacodynamics Administration of cilnidipine has been shown to present an antisympathetic profile in vitro and in vivo. It decreases blood pressure safely and effectively without excessive blood pressure reduction or tachycardia. |
| Molecular Formula |
C27H28N2O7
|
|
|---|---|---|
| Molecular Weight |
492.52
|
|
| Exact Mass |
492.189
|
|
| CAS # |
132203-70-4
|
|
| Related CAS # |
Cilnidipine-d7
|
|
| PubChem CID |
5282138
|
|
| Appearance |
Light yellow to green yellow solid powder
|
|
| Density |
1.2±0.1 g/cm3
|
|
| Boiling Point |
652.6±55.0 °C at 760 mmHg
|
|
| Melting Point |
97-99°C
|
|
| Flash Point |
348.5±31.5 °C
|
|
| Vapour Pressure |
0.0±2.0 mmHg at 25°C
|
|
| Index of Refraction |
1.592
|
|
| LogP |
5.36
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
8
|
|
| Rotatable Bond Count |
11
|
|
| Heavy Atom Count |
36
|
|
| Complexity |
896
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
CC1=C(C(C(=C(N1)C)C(=O)OC/C=C/C2=CC=CC=C2)C3=CC(=CC=C3)[N+](=O)[O-])C(=O)OCCOC
|
|
| InChi Key |
KJEBULYHNRNJTE-DHZHZOJOSA-N
|
|
| InChi Code |
InChI=1S/C27H28N2O7/c1-18-23(26(30)35-14-8-11-20-9-5-4-6-10-20)25(21-12-7-13-22(17-21)29(32)33)24(19(2)28-18)27(31)36-16-15-34-3/h4-13,17,25,28H,14-16H2,1-3H3/b11-8+
|
|
| Chemical Name |
3-O-(2-methoxyethyl) 5-O-[(E)-3-phenylprop-2-enyl] 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.08 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 (5.08 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. View More
Solubility in Formulation 3: 5% DMSO +Corn oil : 7 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0304 mL | 10.1519 mL | 20.3037 mL | |
| 5 mM | 0.4061 mL | 2.0304 mL | 4.0607 mL | |
| 10 mM | 0.2030 mL | 1.0152 mL | 2.0304 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.
Effects of combination therapy with efonidipine or cilnidipine added on ARB on renal outcomes in hypertensive patients with CKD and proteinuria
CTID: UMIN000005359
Phase: Status: Pending
Date: 2011-04-01
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA