Identification
- Summary
Morniflumate is an NSAID derived from niflumic acid used in the symptomatic treatment of inflammatory conditions of the airways, ENT, and the urogenital and osteoarticular systems.
- Generic Name
- Morniflumate
- DrugBank Accession Number
- DB09285
- Background
Morniflumate is a non-steroidal anti-inflammatory drug with antipyretic properties. It is the morpholinoethyl ester of niflumic acid 7. In one study, post morniflumate ingestion, physical examination and clinical symptoms of those with bronchitis showed improvement 1.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Morniflumate (DB09285)
- Weight
- Average: 395.382
Monoisotopic: 395.145676005 - Chemical Formula
- C19H20F3N3O3
- Synonyms
- Morniflumate
- Morniflumato
- External IDs
- UP 164
Pharmacology
- Indication
Morniflumate is indicated for the treatment of inflammatory conditions affecting the airways, ENT system, urogenital tract and bone and joint systems in adults. In Italy, morniflumate is also indicated for the treatment of pain associated with ear, nose, throat (ENT) and gastrointestinal inflammatory conditions in children. Morniflumate is a well established NSAID that has been in use for over three decades in Italy (particularly for the treatment of upper respiratory tract infections in children), France, Belgium, Austria, Switzerland, Spain and Portugal; it has a generally favorable tolerability profile.
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 Symptomatic treatment of Inflammation •••••••••••• ••••• •••••••• •••••••••••• ••••••••••• •••••• Symptomatic treatment of Inflammation •••••••••••• ••••• •••••••• •••••••••••• ••••••••••• •••••• Symptomatic treatment of Inflammation •••••••••••• ••••• •••••••• •••••••••••• ••••••••••• •••••• Symptomatic treatment of Inflammation •••••••••••• ••••• •••••••• •••••••••••• ••••••••••• •••••• Symptomatic treatment of Inflammation •••••••••••• ••••• •••••••• •••••••••••• ••••••••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Morniflumate, given at therapeutic dosages to healthy human volunteers, on leukotriene B4 (LTB4) and thromboxane (TXB2) synthesis, both in purified PMNs (polymorphnuclear neutrophils) and in whole blood 1.
In whole blood experiments, morniflumate reduced blood leukotriene B4 (LTB4) synthesis induced by Ca-ionophore A23187 Bx approximately 50%, both after a single dose and at steady state; the level of inhibition showed a pattern similar to the plasma levels of the bioactive metabolite of morniflumate (M1). The inhibition of serum thromboxane B2 (TXB2) levels was higher than 85%. Hence, morniflumate is demonstrated to reduce arachidonic acid metabolism, by exerting its effects on cyclooxygenase and 5-lipoxygenase. This characteristic might provide a better approach for anti-inflammatory therapy 1.
In several animal models orally administered morniflumate, the beta-morpholinoethyl ester of niflumic acid, proved almost equal to the parent compound in anti-inflammatory, analgesic and antipyretic activity with the absence of gastric irritating/ulcerogenic effects of its acidic parent compound 7.
- Mechanism of action
The primary mechanism of niflumic acid and its ester is action is inhibition of enzymes involved in the synthesis of inflammatory prostaglandins 5. This medication inhibits cyclooxygenase and 5-lipoxygenase pathways, which lead to fever and inflammation 10.
Niflumic acid, a calcium-activated Cl- channel blocker, is an analgesic and anti-inflammatory agent used in the treatment of inflammatory conditions. Niflumic acid does directly inhibit calcium channels or activate potassium channels. Niflumic acid selectively reduces noradrenaline- and 5-HT-induced pressor responses by inhibiting a mechanism which leads to the opening of voltage-gated calcium channels 10. Niflumic acid (NFA) produces biphasic behavior on human CLC-K channels that suggests the presence of two functionally different binding sites: an activating site and a blocking site 10.
Target Actions Organism UArachidonate 5-lipoxygenase antagonistHumans UProstaglandin G/H synthase 2 Not Available Humans ULeukotriene B4 receptor 1 antagonistHumans UThromboxane A2 receptor Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Strongly bound to plasma proteins with approximately 100% bioavailability 9.
- Metabolism
The pharmacokinetic availability of niflumic acid in two different pharmaceutical preparations have been studied in 12 subjects after oral administration 9.
Bioavailability and pharmacokinetics studies after oral and intravenous (IV) administration demonstrate that morniflumate is absorbed as from the gastrointestinal tract, followed by rapid hydrolysis in the plasma, releasing the free acidic form, the molecule responsible for its anti-inflammatory effects. The ester displays gastroprotective effect against the ulcerogenic effects of niflumic acid 7.
- Route of elimination
0.12 L /kg on average 9
- Half-life
2h 9
- Clearance
45 ml/min 9
- Adverse Effects
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As with other anti-inflammatory medications, adverse effects may include: agranulocytosis, bleeding, hepatotoxicity, acute renal failure, dermatoses, and rarely angioedema and urticaria 7.
- 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 softwareAbacavir Morniflumate may decrease the excretion rate of Abacavir which could result in a higher serum level. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Morniflumate is combined with Abciximab. Acebutolol Morniflumate may decrease the antihypertensive activities of Acebutolol. Aceclofenac The risk or severity of adverse effects can be increased when Aceclofenac is combined with Morniflumate. Acemetacin The risk or severity of adverse effects can be increased when Morniflumate is combined with Acemetacin. - Food Interactions
- Not Available
Products
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Categories
- ATC Codes
- M01AX22 — Morniflumate
- Drug Categories
- Acids, Carbocyclic
- Agents causing hyperkalemia
- Agents that produce hypertension
- Aminobenzoates
- Anti-Inflammatory Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Antiinflammatory and Antirheumatic Products
- Antiinflammatory and Antirheumatic Products, Non-Steroids
- Benzene Derivatives
- Benzoates
- Fenamates
- Musculo-Skeletal System
- Nephrotoxic agents
- Nicotinic Acids
- ortho-Aminobenzoates
- Pyridines
- UGT1A9 Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as trifluoromethylbenzenes. These are organofluorine compounds that contain a benzene ring substituted with one or more trifluoromethyl groups.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Trifluoromethylbenzenes
- Direct Parent
- Trifluoromethylbenzenes
- Alternative Parents
- Pyridinecarboxylic acids / Aniline and substituted anilines / Aminopyridines and derivatives / Morpholines / Imidolactams / Vinylogous amides / Heteroaromatic compounds / Trialkylamines / Amino acids and derivatives / Carboxylic acid esters show 10 more
- Substituents
- Alkyl fluoride / Alkyl halide / Amine / Amino acid or derivatives / Aminopyridine / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Azacycle / Carboxylic acid derivative / Carboxylic acid ester show 26 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- R133MWH7X1
- CAS number
- 65847-85-0
- InChI Key
- LDXSPUSKBDTEKA-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H20F3N3O3/c20-19(21,22)14-3-1-4-15(13-14)24-17-16(5-2-6-23-17)18(26)28-12-9-25-7-10-27-11-8-25/h1-6,13H,7-12H2,(H,23,24)
- IUPAC Name
- 2-(morpholin-4-yl)ethyl 2-{[3-(trifluoromethyl)phenyl]amino}pyridine-3-carboxylate
- SMILES
- FC(F)(F)C1=CC(NC2=C(C=CC=N2)C(=O)OCCN2CCOCC2)=CC=C1
References
- General References
- Melica A, Donateo L, Gerardi R, Parenti M: [A new anti-inflammatory-analgesic-antipyretic, morniflumate, in the treatment of chronic recurring bronchitis]. Riv Eur Sci Med Farmacol. 1991 Feb-Apr;13(1-2):51-60. [Article]
- Civelli M, Vigano T, Acerbi D, Caruso P, Giossi M, Bongrani S, Folco GC: Modulation of arachidonic acid metabolism by orally administered morniflumate in man. Agents Actions. 1991 Jul;33(3-4):233-9. [Article]
- Schiantarelli P, Cadel S, Acerbi D: A gastroprotective anti-inflammatory agent: the beta-morpholinoethyl ester of niflumic acid (morniflumate). Agents Actions. 1984 Feb;14(2):247-56. [Article]
- Mano Y, Usui T, Kamimura H: In vitro inhibitory effects of non-steroidal anti-inflammatory drugs on 4-methylumbelliferone glucuronidation in recombinant human UDP-glucuronosyltransferase 1A9--potent inhibition by niflumic acid. Biopharm Drug Dispos. 2006 Jan;27(1):1-6. doi: 10.1002/bdd.475. [Article]
- Sinkkonen ST, Mansikkamaki S, Moykkynen T, Luddens H, Uusi-Oukari M, Korpi ER: Receptor subtype-dependent positive and negative modulation of GABA(A) receptor function by niflumic acid, a nonsteroidal anti-inflammatory drug. Mol Pharmacol. 2003 Sep;64(3):753-63. doi: 10.1124/mol.64.3.753. [Article]
- Morniflumate induced urticaria and angioedema [Link]
- A gastroprotective anti-inflammatory agent: theβ-morpholinoethyl ester of niflumic acid (morniflumate) [Link]
- Modulation of arachidonic acid metabolism by orally administered morniflumate in man [Link]
- The pharmacokinetics and availability of niflumic acid in humans [Link]
- Niflumic acid [Link]
- External Links
- KEGG Drug
- D05078
- PubChem Compound
- 72106
- PubChem Substance
- 310265178
- ChemSpider
- 65089
- 30225
- ChEBI
- 136018
- ChEMBL
- CHEMBL2105059
- ZINC
- ZINC000021999791
- Wikipedia
- Morniflumate
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Suspension Oral 35 MG/ML Granule, for suspension Oral Suspension Oral Tablet Granule, for suspension Oral 350 MG Suppository Rectal 400 MG Suppository Rectal 700 MG Suspension Oral 3.5 % Tablet 350 MG Tablet 700 MG Suppository Rectal - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 75-77 https://www.scbt.com/scbt/product/morniflumate-65847-85-0 water solubility soluble in DMSO https://www.medkoo.com/products/10883 - Predicted Properties
Property Value Source Water Solubility 0.0861 mg/mL ALOGPS logP 3.34 ALOGPS logP 4.77 Chemaxon logS -3.7 ALOGPS pKa (Strongest Acidic) 14.21 Chemaxon pKa (Strongest Basic) 5.86 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 63.69 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 97.79 m3·mol-1 Chemaxon Polarizability 38.37 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes 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 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0249000000-749624adeab8e5eebcd7 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-0419000000-698b8a98cbeae3caf65d Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-02c2-0269000000-8303f2356c4040abbf60 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0295000000-921b85b5521729027492 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-05ur-6976000000-ae9a1141dea5a5589751 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0190000000-f23184c1ed478d3d3a7e 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]- 183.75618 predictedDeepCCS 1.0 (2019) [M+H]+ 186.11418 predictedDeepCCS 1.0 (2019) [M+Na]+ 192.55913 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Iron ion binding
- Specific Function
- Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
- Gene Name
- ALOX5
- Uniprot ID
- P09917
- Uniprot Name
- Arachidonate 5-lipoxygenase
- Molecular Weight
- 77982.595 Da
References
- A gastroprotective anti-inflammatory agent: theβ-morpholinoethyl ester of niflumic acid (morniflumate) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
- Gene Name
- PTGS2
- Uniprot ID
- P35354
- Uniprot Name
- Prostaglandin G/H synthase 2
- Molecular Weight
- 68995.625 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Nucleotide binding
- Specific Function
- Receptor for extracellular ATP > UTP and ADP. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. May be the cardiac P2Y r...
- Gene Name
- LTB4R
- Uniprot ID
- Q15722
- Uniprot Name
- Leukotriene B4 receptor 1
- Molecular Weight
- 37556.925 Da
References
- Modulation of arachidonic acid metabolism by orally administered morniflumate in man [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Thromboxane a2 receptor activity
- Specific Function
- Receptor for thromboxane A2 (TXA2), a potent stimulator of platelet aggregation. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messen...
- Gene Name
- TBXA2R
- Uniprot ID
- P21731
- Uniprot Name
- Thromboxane A2 receptor
- Molecular Weight
- 37430.69 Da
References
- Modulation of arachidonic acid metabolism by orally administered morniflumate in man [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Iron ion binding
- Specific Function
- Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
- Gene Name
- ALOX5
- Uniprot ID
- P09917
- Uniprot Name
- Arachidonate 5-lipoxygenase
- Molecular Weight
- 77982.595 Da
References
- A gastroprotective anti-inflammatory agent: theβ-morpholinoethyl ester of niflumic acid (morniflumate) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
- Gene Name
- PTGS2
- Uniprot ID
- P35354
- Uniprot Name
- Prostaglandin G/H synthase 2
- Molecular Weight
- 68995.625 Da
References
- A gastroprotective anti-inflammatory agent: theβ-morpholinoethyl ester of niflumic acid (morniflumate) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Niflumic acid is the major active metabolite of morniflumate, and this enzyme action was based on the actions of this metabolite on UGT1A9 enzyme.
- General Function
- Retinoic acid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1-9
- Molecular Weight
- 59940.495 Da
References
- Mano Y, Usui T, Kamimura H: In vitro inhibitory effects of non-steroidal anti-inflammatory drugs on 4-methylumbelliferone glucuronidation in recombinant human UDP-glucuronosyltransferase 1A9--potent inhibition by niflumic acid. Biopharm Drug Dispos. 2006 Jan;27(1):1-6. doi: 10.1002/bdd.475. [Article]
- Joo J, Kim YW, Wu Z, Shin JH, Lee B, Shon JC, Lee EY, Phuc NM, Liu KH: Screening of non-steroidal anti-inflammatory drugs for inhibitory effects on the activities of six UDP-glucuronosyltransferases (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) using LC-MS/MS. Biopharm Drug Dispos. 2015 May;36(4):258-64. doi: 10.1002/bdd.1933. Epub 2015 Jan 27. [Article]
Drug created at October 29, 2015 18:08 / Updated at February 03, 2022 06:26