Azelnidipine
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Azelnidipine
- DrugBank Accession Number
- DB09230
- Background
Azelnidipine is a dihydropyridine calcium channel blocker. It is marketed by Daiichi-Sankyo pharmaceuticals, Inc. in Japan. It has a gradual onset of action and produces a long-lasting decrease in blood pressure, with only a small increase in heart rate, unlike some other calcium channel blockers 3. It is currently being studied for post-ischemic stroke management 4.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 582.657
Monoisotopic: 582.247834831 - Chemical Formula
- C33H34N4O6
- Synonyms
- Azelnidipine
- External IDs
- CS-905
Pharmacology
- Indication
For the treatment of hypertension.
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- Pharmacodynamics
Azelnidipine is a vasodilator that induces a gradual decrease in blood pressure in hypertensive patients. Unlike other members of its drug class, azelnidipine does not induce reflex tachycardia due to vasodilation. This is likely due to the fact that it elicits a gradual fall in blood pressure
It also exhibits a prolonged hypotensive effect and has been shown to have a strong anti-arteriosclerotic action in vessels due to its high affinity for vascular tissue and antioxidative activity 2.
Clinical studies have demonstrated that azelnidipine markedly reduced heart rate and proteinuria in hypertensive patients by inhibiting sympathetic nerve activity. Azelnidipine has also been confirmed to have cardio-protective, neuroprotective, and anti-atherosclerotic properties, and has also been found to prevent insulin resistance 2.
- Mechanism of action
Azelnidipine inhibits trans-membrane Ca2+ influx through the voltage-dependent channels of smooth muscles in vascular walls. Ca2+ channels are classified into various categories, including L-type, T-type, N-type, P/Q-type, and R-type Ca2+ channels. The L-type Ca2+ channels 6. Normally, calcium induces smooth muscle contraction, contributing to hypertension. When calcium channels are blocked, the vascular smooth muscle does not contract, resulting in relaxation of vascular smooth muscle walls and decreased blood pressure.
Target Actions Organism UVoltage-dependent L-type calcium channel subunit beta-1 agonistHumans - Absorption
Oral ingestion of azelnidipine demonstrates rapid and dose-dependent absorption 6.
- Volume of distribution
In a Chinese study examining the pharmacokinetics of the drug, the volume of distribution was found to be 1749 +/- 964 7.
- Protein binding
Azelnidipine is widely bound to human plasma proteins (90%–91%) 7.
- Metabolism
Like most members of its class, azelnidipine primarily undergoes first-pass hepatic metabolism. Azelnidipine is metabolized by hepatic cytochrome P450 (CYP) 3A4 and has no active metabolite product. It may interact with other drugs or compounds that are substrates for this enzyme.
Azelnidipine is lipophilic and has a potent affinity for membranes of vascular smooth muscle cells 6.
- Route of elimination
In one study, following a single 4mg oral dose of 14C-labeled azelnidipine in humans, about 26% of the drug was thought to br excreted in the urine and 63% in the feces during the 1 week period post administration 2.
- Half-life
16 –28 hours 7.
- Clearance
Not Available
- Adverse Effects
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- Toxicity
As with any calcium channel blocker toxicity, bradycardia and hypotension may result from overdose. The treatment of patients with bradycardia and hypotension begins with supportive therapy and atropine, however, patients with severe toxicity do not have an adequate response and must be managed more aggressively.
Calcium plays an imperative role in myocardial contractility, automaticity and vascular tone. Administration of exogenous calcium is of benefit in cases of toxicity 8.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Azelnidipine can be increased when it is combined with Abametapir. Acarbose The risk or severity of hypoglycemia can be increased when Azelnidipine is combined with Acarbose. Acebutolol Acebutolol may increase the arrhythmogenic activities of Azelnidipine. Aceclofenac The risk or severity of hyperkalemia can be increased when Aceclofenac is combined with Azelnidipine. Acemetacin The risk or severity of hyperkalemia can be increased when Azelnidipine is combined with Acemetacin. - 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
- Azelnidipine Chemipha / Azelnidipine FFP / Azelnidipine JG / Azelnidipine KOG / Azelnidipine Nichi-Iko / Azelnidipine Tanabe / Azelnidipine TCK / Azelnidipine Teva / Azelnidipine Towa / Azelnidipine YD / Beiqi / Calblock / Rezaldas HD / Rezaltas LD
Categories
- Drug Categories
- Acids, Acyclic
- Agents causing hyperkalemia
- Amino Acids
- Amino Acids, Cyclic
- Amino Acids, Peptides, and Proteins
- Antiarrhythmic agents
- Azetidines
- Azetines
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Imines
- Imino Acids
- Pyridines
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Diphenylmethanes
- Direct Parent
- Diphenylmethanes
- Alternative Parents
- Dihydropyridinecarboxylic acids and derivatives / Nitrobenzenes / Nitroaromatic compounds / Aralkylamines / Dicarboxylic acids and derivatives / Vinylogous amides / Enoate esters / Trialkylamines / Amino acids and derivatives / Azetidines show 11 more
- Substituents
- Allyl-type 1,3-dipolar organic compound / Alpha,beta-unsaturated carboxylic ester / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Azetidine / C-nitro compound / Carbonyl group show 30 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- PV23P19YUG
- CAS number
- 123524-52-7
- InChI Key
- ZKFQEACEUNWPMT-UHFFFAOYSA-N
- InChI
- InChI=1S/C33H34N4O6/c1-20(2)42-32(38)27-21(3)35-31(34)29(28(27)24-15-10-16-25(17-24)37(40)41)33(39)43-26-18-36(19-26)30(22-11-6-4-7-12-22)23-13-8-5-9-14-23/h4-17,20,26,28,30,35H,18-19,34H2,1-3H3
- IUPAC Name
- 3-[1-(diphenylmethyl)azetidin-3-yl] 5-propan-2-yl 2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
- SMILES
- CC(C)OC(=O)C1=C(C)NC(N)=C(C1C1=CC=CC(=C1)[N+]([O-])=O)C(=O)OC1CN(C1)C(C1=CC=CC=C1)C1=CC=CC=C1
References
- Synthesis Reference
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245158/
- General References
- Oizumi K, Nishino H, Koike H, Sada T, Miyamoto M, Kimura T: Antihypertensive effects of CS-905, a novel dihydropyridine Ca++ channel blocker. Jpn J Pharmacol. 1989 Sep;51(1):57-64. [Article]
- Nada T, Nomura M, Koshiba K, Kawano T, Mikawa J, Ito S: Clinical study with azelnidipine in patients with essential hypertension. Antiarteriosclerotic and cardiac hypertrophy-inhibitory effects and influence on autonomic nervous activity. Arzneimittelforschung. 2007;57(11):698-704. doi: 10.1055/s-0031-1296670. [Article]
- DRUG: Azelnidipine [Link]
- Azelnidipine, a long-acting calcium channel blocker, could control hypertension without decreasing cerebral blood flow in post-ischemic stroke patients. A 123I-IMP SPECT follow-up study [Link]
- Azelnidipine MSDS [Link]
- Clinical use of azelnidipine in the treatment of hypertension in Chinese patients [Link]
- Determination of azelnidipine by LC–ESI-MS and its application to a pharmacokinetic study in healthy Chinese volunteers [Link]
- Calcium Channel Blocker Poisoning [Link]
- External Links
- KEGG Drug
- D01145
- PubChem Compound
- 65948
- PubChem Substance
- 310265134
- ChemSpider
- 59352
- ChEBI
- 31247
- ChEMBL
- CHEMBL1275868
- Wikipedia
- Azelnidipine
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Treatment Hypertension / Obstructive Sleep Apnea (OSA) 1 somestatus stop reason just information to hide 4 Completed Prevention Cardiovascular Disease (CVD) / Diabetes / Hypertension 1 somestatus stop reason just information to hide 4 Completed Prevention Cardiovascular Disease (CVD) / Hypertension 1 somestatus stop reason just information to hide 4 Completed Prevention Coronary Artery Atherosclerosis / Hypertension 1 somestatus stop reason just information to hide 4 Completed Treatment Hypertension 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 193-195 [L1381] water solubility Insoluble in water Not Available - Predicted Properties
Property Value Source Water Solubility 0.00082 mg/mL ALOGPS logP 5.12 ALOGPS logP 5.57 Chemaxon logS -5.8 ALOGPS pKa (Strongest Acidic) 19.88 Chemaxon pKa (Strongest Basic) 6 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 137.03 Å2 Chemaxon Rotatable Bond Count 11 Chemaxon Refractivity 172.06 m3·mol-1 Chemaxon Polarizability 60.76 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 0 Chemaxon Rule of Five No 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 splash10-0159-0900060000-c80c65ee0493cbc50569 - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 225.75972 predictedDeepCCS 1.0 (2019) [M+H]+ 227.5846 predictedDeepCCS 1.0 (2019) [M+Na]+ 233.19043 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Regulatory subunit of L-type calcium channels (PubMed:1309651, PubMed:15615847, PubMed:8107964). Regulates the activity of L-type calcium channels that contain CACNA1A as pore-forming subunit (By similarity). Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit and increases the presence of the channel complex at the cell membrane (PubMed:15615847). Required for functional expression L-type calcium channels that contain CACNA1D as pore-forming subunit (PubMed:1309651). Regulates the activity of L-type calcium channels that contain CACNA1B as pore-forming subunit (PubMed:8107964)
- Specific Function
- high voltage-gated calcium channel activity
- Gene Name
- CACNB1
- Uniprot ID
- Q02641
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit beta-1
- Molecular Weight
- 65712.995 Da
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- DRUG: Azelnidipine [Link]
Drug created at October 23, 2015 16:13 / Updated at February 03, 2022 06:25