Meclofenamic Acid's primary mechanism of action is the inhibition of prostaglandin biosynthesis. It achieves this by blocking the activity of cyclooxygenase (COX) enzymes, which are key in the conversion of arachidonic acid to prostaglandins. This action reduces the production of inflammatory mediators, leading to its analgesic and anti-inflammatory effects. It has also been identified as a "balanced" inhibitor, suggesting it may have a well-characterized interaction with its target enzymes.

Meclofenamic acid inhibits FTO demethylation in a dose-response manner (0-100 μM, 24 hours) [1]. Meclofenamic acid suppresses prostaglandin synthesis by inhibiting cyclooxygenase, having an IC50 of about 1 μM [2]. Meclofenamic acid counteracts tissue reactions to certain prostaglandins and suppresses the production of 5-HETE and LTB4 from human neutrophils when induced by calcium ionophores [2].
In vitro, Meclofenamic Acid is characterized by its ability to inhibit prostaglandin biosynthesis. Its activity can be assessed in cell-based systems by measuring the production of prostaglandins or other inflammatory mediators in the presence of the compound. It is a well-established NSAID, and its in vitro profile includes its potency as a COX inhibitor. It is also studied for its effects on ion channels and cancer-related pathways.

In vivo, Meclofenamic Acid is used for its analgesic and anti-inflammatory effects in conditions like arthritis, dysmenorrhea, and muscle pain. Its in vivo activity is a result of its systemic inhibition of prostaglandin synthesis. It is an effective NSAID for managing mild to moderate pain and inflammation.

In vitro enzyme/receptor binding studies for Meclofenamic Acid would typically involve measuring its ability to inhibit the COX-1 and COX-2 enzymes. In these assays, the enzyme is incubated with its substrate (arachidonic acid) in the presence of varying concentrations of the compound. The inhibition of prostaglandin production is then measured, and the IC50 value is calculated. This is the standard method for characterizing the mechanism of action of NSAIDs.

Western Blot Analysis[1]
Cell Types: HeLa Cell
Tested Concentrations: 0, 12.5, 25, 50, 100 μM
Incubation Duration: 24 h
Experimental Results: Inhibited FTO demethylation in a dose-response manner and increased the level of m6A in cellular mRNA Targeting FTO.
In vitro cellular assays for Meclofenamic Acid are used to study its effects on cells. In immune cells, its ability to inhibit the production of prostaglandins and other inflammatory mediators can be measured. In cancer cells, its effects on cell proliferation and apoptosis are studied to explore its potential in cancer-related pathways. These assays confirm its mechanism as a COX inhibitor and its potential for other applications.

In vivo animal studies for Meclofenamic Acid are standard for NSAIDs. These studies typically involve models of inflammation and pain, such as the carrageenan-induced paw edema model or the formalin test. Animals are treated with the compound, and the reduction in inflammation or pain response is measured. These studies confirm its efficacy and are used to determine its therapeutic index.

Absorption, Distribution and Excretion
Meclofenamic acid is rapidly absorbed by the body after a single or multiple oral dose, with peak plasma concentrations reached within 0.5 to 2 hours. Concomitant use of antacids (aluminum hydroxide and magnesium hydroxide) does not interfere with its absorption. Unlike most nonsteroidal anti-inflammatory drugs (NSAIDs), which show a reduced absorption rate but not necessarily a decrease in the extent of absorption when taken with food, meclofenamic acid exhibits both a reduced absorption rate and an decreased extent of absorption when taken with food. It has been reported that taking meclofenamic acid capsules half an hour after a meal reduces average bioavailability by 26%, decreases average peak concentration (Cmax) by four times, and delays the time to peak concentration by 3 hours. Other metabolites (with unknown excretion rates) comprise 35% to 62% of the remaining dose and are excreted in the urine. The remaining dose (approximately 30%) is excreted in the feces (apparently via bile). Trace amounts of meclofenamic acid sodium are secreted into human breast milk.
9.1 to 43.2 liters
Oral clearance = 206 mL/min
Metabolism/Metabolites

Hepatic metabolism. Meclofenamic acid is extensively metabolized into one active metabolite (metabolite I; the 3-hydroxymethyl metabolite of meclofenamic acid) and at least six other minor metabolites with less well-defined characteristics. In vitro studies have shown that only metabolite I inhibits cyclooxygenase activity, with an activity approximately one-fifth that of meclofenamic acid.
Biological half-life

A study in 10 healthy subjects showed that the apparent elimination half-life after a single oral dose ranged from 0.8 to 5.3 hours. The mean half-life of metabolite I (the 3-hydroxymethyl metabolite of meclofenamic acid) is approximately 15 hours.
Pharmacokinetic properties of Meclofenamic Acid include a molecular weight of 296.15 g/mol and a molecular formula of C14H11Cl2NO2. It is an anthranilic acid derivative. Its ADME (absorption, distribution, metabolism, excretion) properties are characteristic of NSAIDs. It is typically administered orally.

Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation
Since there is currently no information regarding the use of meclofenamic acid during lactation, alternative medications may be preferred, especially for breastfed newborns or premature infants. ◉ Effects on Breastfed Infants
No published information found as of the revision date. ◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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Protein Binding
Over a wide range of drug concentrations, the binding rate to plasma proteins is greater than 99%.
As an NSAID, Meclofenamic Acid can cause side effects such as gastrointestinal irritation, ulceration, and bleeding. It may also affect kidney function. It is contraindicated in patients with a history of peptic ulcer disease or severe renal impairment. Long-term use requires monitoring. Specific toxicity data are not detailed in the provided sources, but its safety profile is similar to other drugs in its class.

[1]. Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5. Nucleic Acids Res. 2015 Jan;43(1):373-84.

[2]. Pharmacology, pharmacokinetics, and therapeutic use of meclofenamate sodium. Clin J Pain. 1991;7 Suppl 1:S44-8.

[3]. Inhibition of hKv2.1, a major human neuronal voltage-gated K+ channel, by meclofenamic acid. Eur J Pharmacol. 1999 Aug 13;378(3):349-56.

[4]. Meclofenamic acid improves the signal to noise ratio for visual responses produced by ectopicexpression of human rod opsin. Mol Vis. 2017 Jun 16;23:334-345. eCollection 2017.

Meclofenamic acid is an aminobenzoic acid, a derivative of anthranilic acid, in which a hydrogen atom bonded to a nitrogen atom is replaced by 2,6-dichloro-3-methylphenyl. It is a nonsteroidal anti-inflammatory drug (NSAID), and its sodium salt is used to treat dysmenorrhea, osteoarthritis, and rheumatoid arthritis. It possesses a variety of pharmacological effects, including NSAID, antirheumatic, antitumor, anticonvulsant, analgesic, antipyretic, EC 1.13.11.34 (arachidonic acid 5-lipoxygenase) inhibitor, and EC 1.14.99.1 (prostaglandin endoperoxidase) inhibitor. It is an aminobenzoic acid, a secondary amino compound, and an organochlorine compound. It is the conjugate acid of meclofenamic acid (1-). It is a NSAID with antipyretic and antigranulomatous effects. It also inhibits prostaglandin biosynthesis. It also inhibits prostaglandin biosynthesis.
See also: Meclofenamic acid sodium (in salt form).
Indications
For the relief of mild to moderate pain, and for the treatment of primary dysmenorrhea and idiopathic menorrhagia. It can also be used to relieve the signs and symptoms of acute and chronic rheumatoid arthritis and osteoarthritis.
Mechanism of Action
Like other nonsteroidal anti-inflammatory drugs (NSAIDs), its mechanism of action is not fully understood. Its therapeutic effect does not stem from stimulation of the pituitary-adrenal axis. Animal studies have shown that meclofenamic acid inhibits prostaglandin synthesis and competes with prostaglandin receptors for binding sites. In vitro studies have shown that meclofenamic acid inhibits the activity of human leukocyte 5-lipoxygenase. These properties may explain the anti-inflammatory effect of meclofenamic acid. There is currently no evidence that meclofenamic acid alters the course of the primary disease.

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Pharmacodynamics
Meclofenamic acid is a nonsteroidal anti-inflammatory drug (NSAID) that has been shown to have anti-inflammatory, analgesic, and antipyretic effects in experimental animals.
Meclofenamic Acid is a non-steroidal anti-inflammatory drug (NSAID) with analgesic, antipyretic, and anti-inflammatory properties. Its CAS number is 644-62-2. It is also known as meclofenamate. It has been used for the treatment of arthritis, dysmenorrhea, and muscle pain. In addition to its anti-inflammatory effects, it is being studied for its potential in biomedical research, including ion channel modulation and cancer-related pathways.

C14H11CL2NO2

296.15

295.016

644-62-2

Meclofenamic acid sodium;6385-02-0;Meclofenamic acid sodium hydrate;67254-91-5;Meclofenamic acid-d4;1185072-18-7;Meclofenamic acid-13C6

4037

White to yellow solid powder

1.4±0.1 g/cm3

399.4±42.0 °C at 760 mmHg

257-259ºC

195.3±27.9 °C

0.0±1.0 mmHg at 25°C

1.663

6.67

2

3

3

19

327

0

SBDNJUWAMKYJOX-UHFFFAOYSA-N

InChI=1S/C14H11Cl2NO2/c1-8-6-7-10(15)13(12(8)16)17-11-5-3-2-4-9(11)14(18)19/h2-7,17H,1H3,(H,18,19)

2-(2,6-dichloro-3-methylanilino)benzoic acid

INF-4668CI 583INF4668 CI-583Meclonax Meclomen Meclodium

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

MEthanol : ~7.14 mg/mL (~24.11 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)