Manidipine
Identification
- Name
- Manidipine
- Accession Number
- DB09238
- Description
Manidipine (INN) is a calcium channel blocker (dihydropyridine type) that is used clinically as an antihypertensive. It is selective for vasculature and does not produce effects on the heart at clinically relevant dosages.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Manidipine (DB09238)
- Weight
- Average: 610.711
Monoisotopic: 610.27913496 - Chemical Formula
- C35H38N4O6
- Synonyms
- Manidipine
- Manidipino
Pharmacology
- Indication
For the treatment of hypertension.
- Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More- Pharmacodynamics
Manidipine produces vasodilation resulting in lower blood pressure 1.
- Mechanism of action
Contraction of vascular smooth muscle is stimulated by Gq coupled receptors which produce calcium release from the sarcoplasmic reticulum. This is followed by opening of voltage dependent calcium channels and an influx of calcium into the cell ultimately producing contraction. Manidipine binds to and dissociates slowly from L- and T-type voltage dependent calcium channels on smooth muscle cells, blocking the entrance of extracellular calcium into the cell and preventing this contraction 1,2. This produces vasodilation which decreases blood pressure. Manidipine produces renal vasodilation and an increase in natriuresis. This likely contributes to the antihypertensive effect by reducing blood volume. Manidipine is selective for the vasculature and does not produce significant effects on the heart or central nervous system at clinically relevant dosages.
Target Actions Organism AVoltage-dependent L-type calcium channel blockerHumans AVoltage-dependent T-type calcium channel blockerHumans - Absorption
The median Tmax is 1.5 h 1. Administration with food produces an 1.3-1.6-fold increase in Cmax but no change in Tmax. Manidipine does not accumulate significantly with multiple doses.
- Volume of distribution
- Not Available
- Protein binding
Manidipine is 99% bound to human plasma proteins 1.
- Metabolism
Manidipine is extensively metabolized by CYP enzymes to pyridine derivatives and diphenylmethane derivatives which make up 4-7% and 22-24% of the dose excreted in the urine 1.
- Route of elimination
Manidipine is eliminated through extensive metabolism. 63% is eliminated in the feces and 31% in the urine as metabolites 1.
- Half-life
The half life of elimination has been observed to be dose dependent 1. Doses of 5, 10, and 20 mg produced half lives of 3.94, 5.02, and 7.95 h respectively.
- Clearance
- Not Available
- Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More- Toxicity
The most common adverse events reported in clinical trials were ankle oedema (6%), headache (3.8%), palpitation (2.7%), flushing (2.2%), dizziness (1.6%), rash (0.5%) and fatigue (0.5%) 1.
- Affected organisms
- Humans and other mammals
- 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 Unlock Additional DataAbametapir The serum concentration of Manidipine can be increased when it is combined with Abametapir. Abiraterone The metabolism of Abiraterone can be decreased when combined with Manidipine. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Manidipine. Acarbose The risk or severity of hypoglycemia can be increased when Manidipine is combined with Acarbose. Acebutolol The metabolism of Acebutolol can be decreased when combined with Manidipine. Aceclofenac The therapeutic efficacy of Manidipine can be decreased when used in combination with Aceclofenac. Acemetacin The therapeutic efficacy of Manidipine can be decreased when used in combination with Acemetacin. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Manidipine. Acetaminophen The metabolism of Manidipine can be decreased when combined with Acetaminophen. Acetohexamide The metabolism of Acetohexamide can be decreased when combined with Manidipine. Additional Data Available- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - Severity
- Evidence Level
- ActionAction
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Learn more
- Food Interactions
- Not Available
Products
- Product Ingredients
Ingredient UNII CAS InChI Key Manidipine dihydrochloride ZL507UZ6QL 89226-75-5 JINNGBXKBDUGQT-UHFFFAOYSA-N - International/Other Brands
- Manyper
Categories
- ATC Codes
- C08CA11 — Manidipine
- C08CA — Dihydropyridine derivatives
- C08C — SELECTIVE CALCIUM CHANNEL BLOCKERS WITH MAINLY VASCULAR EFFECTS
- C08 — CALCIUM CHANNEL BLOCKERS
- C — CARDIOVASCULAR SYSTEM
- Drug Categories
- ACE Inhibitors and Calcium Channel Blockers
- Agents causing hyperkalemia
- Antiarrhythmic agents
- Antihypertensive Agents
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Calcium-Regulating Hormones and Agents
- Cardiovascular Agents
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (weak)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (moderate)
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Dihydropyridine Derivatives
- 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 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 / N-alkylpiperazines / Dicarboxylic acids and derivatives / Vinylogous amides / Enoate esters / Methyl esters / Amino acids and derivatives show 11 more
- Substituents
- 1,4-diazinane / Allyl-type 1,3-dipolar organic compound / Alpha,beta-unsaturated carboxylic ester / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / C-nitro compound / Carbonyl group show 32 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
Chemical Identifiers
- UNII
- 6O4754US88
- CAS number
- 89226-50-6
- InChI Key
- ANEBWFXPVPTEET-UHFFFAOYSA-N
- InChI
- InChI=1S/C35H38N4O6/c1-24-30(34(40)44-3)32(28-15-10-16-29(23-28)39(42)43)31(25(2)36-24)35(41)45-22-21-37-17-19-38(20-18-37)33(26-11-6-4-7-12-26)27-13-8-5-9-14-27/h4-16,23,32-33,36H,17-22H2,1-3H3
- IUPAC Name
- 3-{2-[4-(diphenylmethyl)piperazin-1-yl]ethyl} 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
- SMILES
- COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)N(=O)=O)C(=O)OCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=CC=C1
References
- General References
- Cheer SM, McClellan K: Manidipine: a review of its use in hypertension. Drugs. 2001;61(12):1777-99. [PubMed:11693466]
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [PubMed:15329044]
- External Links
- PubChem Compound
- 4008
- PubChem Substance
- 347827830
- ChemSpider
- 3868
- 29275
- ChEBI
- 135849
- ChEMBL
- CHEMBL1085699
- Wikipedia
- Manidipine
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Cardiovascular Heart Disease / Chronic Kidney Disease (CKD) / Hypertension,Essential / Stroke 1 4 Terminated Treatment High Blood Pressure (Hypertension) 1 3 Completed Diagnostic Type 2 Diabetes Mellitus 1 3 Completed Treatment High Blood Pressure (Hypertension) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 10 MG Tablet Oral 20 MG Tablet Oral 30 MG Tablet 10 MG Tablet 20 MG Tablet 30 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility <1mg/mL MSDS - Predicted Properties
Property Value Source Water Solubility 0.000995 mg/mL ALOGPS logP 5.11 ALOGPS logP 5.19 ChemAxon logS -5.8 ALOGPS pKa (Strongest Acidic) 19.47 ChemAxon pKa (Strongest Basic) 7.89 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 7 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 116.93 Å2 ChemAxon Rotatable Bond Count 12 ChemAxon Refractivity 175.13 m3·mol-1 ChemAxon Polarizability 65.72 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
- Not Available
Targets
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Blocker
- 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
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [PubMed:15329044]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Blocker
- General Function
- Scaffold protein binding
- 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
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [PubMed:15329044]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Unknown if inhibition is clinically relevant.
- General Function
- Steroid 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 oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [PubMed:15329044]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Unknown if inhibition is clinically relevant.
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [PubMed:15329044]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Vitamin d 24-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 oxidizes a variety of structurally un...
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [PubMed:15329044]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid 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 oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [PubMed:15329044]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [PubMed:15329044]
- Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T: Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52. [PubMed:10805063]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [PubMed:15329044]
Drug created on October 23, 2015 10:51 / Updated on June 12, 2020 10:52
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