Identification
- Summary
Cilnidipine is a dihydropyridine calcium channel blocker with action on both N- and L-type calcium channels used to treat hypertension.
- Generic Name
- Cilnidipine
- DrugBank Accession Number
- DB09232
- Background
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.1
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Cilnidipine (DB09232)
- Weight
- Average: 492.528
Monoisotopic: 492.18965125 - Chemical Formula
- C27H28N2O7
- Synonyms
- Cilnidipine
Pharmacology
- Indication
Cilnidipine is indicated for the management of hypertension for end-organ protection.5 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.6
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of High blood pressure (hypertension) •••••••••••• ••••••• •••••• - Contraindications & Blackbox Warnings
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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.2
- 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.2
Target Actions Organism AVoltage-dependent N-type calcium channel subunit alpha-1B antagonistHumans AVoltage-dependent L-type calcium channel antagonistHumans - Absorption
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.8
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.10
- Volume of distribution
Drugs on the group of dihydropyridines such as cilnidipine tend to have a large volume of distribution.4
- Protein binding
Cilnidipine presents a very high protein binding that represents to even 98% of the administered dose.8
- Metabolism
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.7
- Route of elimination
Cilnidipine gets eliminated through the urine in a proportion of 20% of the administered dose and 80% is eliminated by the feces.7
- Half-life
The half-life of the hypotensive effect for cilnidipine is of about 20.4 min.3
- Clearance
Not Available
- Adverse Effects
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The percentage of reports of cilnidipine that express drug toxicity reported as side effects are 5.26%.9
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbaloparatide The risk or severity of adverse effects can be increased when Abaloparatide is combined with Cilnidipine. Abametapir The serum concentration of Cilnidipine can be increased when it is combined with Abametapir. Acarbose The risk or severity of hypoglycemia can be increased when Cilnidipine is combined with Acarbose. Acebutolol Acebutolol may increase the arrhythmogenic activities of Cilnidipine. Aceclofenac The risk or severity of hyperkalemia can be increased when Aceclofenac is combined with Cilnidipine. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Atelec (Ajinomoto Pharmaceuticals Co. Ltd) / Cilogard (Cipla Ltd)
Categories
- ATC Codes
- C08CA14 — Cilnidipine
- Drug Categories
- Agents causing hyperkalemia
- Antiarrhythmic agents
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Calcium-Regulating Hormones and Agents
- Cardiovascular Agents
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Dihydropyridine Derivatives
- Hypotensive Agents
- Membrane Transport Modulators
- Pyridines
- Selective Calcium Channel Blockers With Mainly Vascular Effects
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dihydropyridinecarboxylic acids and derivatives. These are compounds containing a dihydropyridine moiety bearing a carboxylic acid group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyridines and derivatives
- Sub Class
- Hydropyridines
- Direct Parent
- Dihydropyridinecarboxylic acids and derivatives
- Alternative Parents
- Nitrobenzenes / Styrenes / Nitroaromatic compounds / Dicarboxylic acids and derivatives / Vinylogous amides / Enoate esters / Amino acids and derivatives / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Dialkyl ethers show 8 more
- Substituents
- Allyl-type 1,3-dipolar organic compound / Alpha,beta-unsaturated carboxylic ester / Amine / Amino acid or derivatives / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / C-nitro compound / Carbonyl group / Carboxylic acid derivative show 26 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- dihydropyridine (CHEBI:31399)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 97T5AZ1JIP
- CAS number
- 132203-70-4
- InChI Key
- KJEBULYHNRNJTE-DHZHZOJOSA-N
- InChI
- 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+
- IUPAC Name
- 3-(2-methoxyethyl) 5-(2E)-3-phenylprop-2-en-1-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
- SMILES
- COCCOC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC(=C1)[N+]([O-])=O)C(=O)OC\C=C\C1=CC=CC=C1
References
- General References
- Yoshimoto R, Dohmoto H, Yamada K, Goto A: Prolonged inhibition of vascular contraction and calcium influx by the novel 1,4-dihydropyridine calcium antagonist cinaldipine (FRC-8653). Jpn J Pharmacol. 1991 Jun;56(2):225-9. [Article]
- Lee J, Lee H, Jang K, Lim KS, Shin D, Yu KS: Evaluation of the pharmacokinetic and pharmacodynamic drug interactions between cilnidipine and valsartan, in healthy volunteers. Drug Des Devel Ther. 2014 Oct 8;8:1781-8. doi: 10.2147/DDDT.S68574. eCollection 2014. [Article]
- Uneyama H, Uchida H, Konda T, Yoshimoto R, Akaike N: Selectivity of dihydropyridines for cardiac L-type and sympathetic N-type Ca2+ channels. Eur J Pharmacol. 1999 May 28;373(1):93-100. [Article]
- Henrich W. (2012). Principles and practice of dialysis. Lippincott, Williams & Wilkins.
- Centapres monograph [Link]
- Hypertension Canada [Link]
- Kerala medical journal [Link]
- Lloyd healthcare [Link]
- Medfacts [Link]
- ResearchGate article [Link]
- External Links
- KEGG Drug
- D01173
- PubChem Compound
- 5282138
- PubChem Substance
- 310265136
- ChemSpider
- 4445338
- BindingDB
- 50101813
- ChEBI
- 31399
- ChEMBL
- CHEMBL452076
- Wikipedia
- Cilnidipine
- MSDS
- Download (52.4 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Hypertension / Syndrome, Metabolic 1 4 Unknown Status Treatment Autosomal Dominant Polycystic Kidney Disease （ADPKD) 1 3 Completed Treatment Hypertension 1 3 Completed Treatment Hypertension / Stroke 1 2 Unknown Status Treatment Autosomal Dominant Polycystic Kidney Disease （ADPKD) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated 10 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 110ºC 'MSDS' boiling point (°C) 653ºC 'MSDS' water solubility Insoluble 'MSDS' logP 4.70 'MSDS' pKa 11.39 'MSDS' - Predicted Properties
Property Value Source Water Solubility 0.000566 mg/mL ALOGPS logP 4.39 ALOGPS logP 4.1 Chemaxon logS -5.9 ALOGPS pKa (Strongest Acidic) 19.46 Chemaxon pKa (Strongest Basic) -4.1 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 117 Å2 Chemaxon Rotatable Bond Count 12 Chemaxon Refractivity 137.14 m3·mol-1 Chemaxon Polarizability 51.97 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key MS/MS Spectrum - , positive LC-MS/MS splash10-014i-0012490000-56c247612ff7c5dfa146 MS/MS Spectrum - , positive LC-MS/MS splash10-014i-2915100000-4bb1d47549a538dcee61 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 215.4611 predictedDeepCCS 1.0 (2019) [M+H]+ 217.35649 predictedDeepCCS 1.0 (2019) [M+Na]+ 224.53725 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
- Gene Name
- CACNA1B
- Uniprot ID
- Q00975
- Uniprot Name
- Voltage-dependent N-type calcium channel subunit alpha-1B
- Molecular Weight
- 262493.84 Da
References
- Lee J, Lee H, Jang K, Lim KS, Shin D, Yu KS: Evaluation of the pharmacokinetic and pharmacodynamic drug interactions between cilnidipine and valsartan, in healthy volunteers. Drug Des Devel Ther. 2014 Oct 8;8:1781-8. doi: 10.2147/DDDT.S68574. eCollection 2014. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Components:
References
- Lee J, Lee H, Jang K, Lim KS, Shin D, Yu KS: Evaluation of the pharmacokinetic and pharmacodynamic drug interactions between cilnidipine and valsartan, in healthy volunteers. Drug Des Devel Ther. 2014 Oct 8;8:1781-8. doi: 10.2147/DDDT.S68574. eCollection 2014. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Uesawa Y, Takeuchi T, Mohri K: Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17. [Article]
- Liu XQ, Zhao Y, Li D, Qian ZY, Wang GJ: Metabolism and metabolic inhibition of cilnidipine in human liver microsomes. Acta Pharmacol Sin. 2003 Mar;24(3):263-8. [Article]
Drug created at October 23, 2015 16:20 / Updated at May 05, 2021 20:31