Mefenamic acid Chemical Properties

Melting point:

230 °C

Boiling point:

384.06°C (rough estimate)

Density 

1.0944 (rough estimate)

refractive index 

1.5200 (estimate)

storage temp. 

2-8°C

solubility 

Practically insoluble in water, slightly soluble in ethanol (96 per cent) and in methylene chloride. It dissolves in dilute solutions of alkali hydroxides

pka

4.2(at 25℃)

color 

White to Pale Yellow

Water Solubility 

It is soluble in acetone, chloroform, dichloromethane, methanol. Insoluble in water.

Merck 

14,5798

InChIKey

HYYBABOKPJLUIN-UHFFFAOYSA-N

LogP

5.120

CAS DataBase Reference

61-68-7(CAS DataBase Reference)

NIST Chemistry Reference

Mefenamic acid(61-68-7)

Safety Information

Hazard Codes 

Xn

Risk Statements 

22-40-20/21/22

Safety Statements 

22-36

WGK Germany 

3

RTECS 

CB4550000

HS Code 

28142000

Hazardous Substances Data

61-68-7(Hazardous Substances Data)

Toxicity

LD50 orally in mice, rats: 630, 790 mg/kg (Jahn, Adrian)

MSDS

• Language:English Provider:2-[(2,3-Dimethylphenyl)amino]benzoic acid
• Language:English Provider:SigmaAldrich

Mefenamic acid Usage And Synthesis

Description

Mefenamic acid is a kind of nonsteroidal anti-inflammatory (NSAID) drug belonging to the anthranilic acid derivatives class. It is mainly used for the short-term treatment of mild to moderate pain from various conditions. It is also used for reducing the pain and blood loss from menstrual condition as well as prevention of migraines. Moreover, it may also be used for treating gout attacks. Its mechanism is through inhibiting both the isoforms of COX and preventing the formation of prostaglandins. It is manufactured from 2-chlorobenzoic acid and 2,3-dimethylaniline. 

References

http://www.webmd.com/drugs/2/drug-11586/mefenamic-acid-oral/details
https://en.wikipedia.org/wiki/Mefenamic_acid

Chemical Properties

white or light yellow crystalline powder, odorless, insoluble in water, slightly soluble in ethanol, chloroform, slightly soluble in ether. Melting point 230-231°C, mefenamic acid is an anti-inflammatory analgesic with antipyretic, analgesic and anti-inflammatory effects.

Originator

Ponstan,Parke Davis,UK,1963

Uses

Mefenamic acid is used for the same indications as flufenamic acid. Synonyms for this drug are parkemed, ponstan, ponstel, and others.

Uses

For the treatment of rheumatoid arthritis, osteoarthritis, dysmenorrhea, and mild to moderate pain, inflammation, and fever.

Definition

ChEBI: An aminobenzoic acid that is anthranilic acid in which one of the hydrogens attached to the nitrogen is replaced by a 2,3-dimethylphenyl group. Although classed as a non-steroidal anti-inflammatory drug, its anti-inflammatory properties are considered to b minor. It is used to relieve mild to moderate pain, including headaches, dental pain, osteoarthritis and rheumatoid arthritis.

Indications

Mefenamic acid (Ponstel) is indicated only for analgesia and primary dysmenorrhea when therapy will not exceed 1 week.

Manufacturing Process

A mixture of 800 g of potassium o-bromo-benzoate, 1,500 ml of bis-(2- methoxyethyl)ether, 355 g of N-ethyl-morpholine, 375 g of 2,3- dimethylaniline, and 30 g of cupric acetate is heated gradually with stirring to 140°C over a period of 90 minutes. The hot reaction mixture is then acidified with 260 mi of concentrated hydrochloric acid and the acidified mixture divided into 2 equal portions. One liter of water is added to each portion and the mixtures allowed to cool. The N-(2,3-dimethylphenyl)anthranilic acid which separates upon cooling is collected by filtration and recrystallized from bis(2-methoxyethyl)ether; MP 229° to 230°C (corr.).

brand name

Ponstel (Sciele, Parke Davis, USA), Lysalgo (SIT, Italy), Opustan (Opus Pharm, UK), Parkemed (Parke Davis, Germany), Ponstan (Werner-Lambert, Switzerland), Pontal (Sankyo, Japan).

Therapeutic Function

Analgesic

Synthesis Reference(s)

The Journal of Organic Chemistry, 45, p. 2127, 1980 DOI: 10.1021/jo01299a020

General Description

Mefenamic acid (Ponstel, Ponstan) is one of the oldestNSAIDs, introduced into the market in 1967 for mild tomoderate pain and for primary dysmenorrhea. It is rapidly absorbed with peak plasma levels occurring 2 to 4 hoursafter oral administration. It undergoes hepatic benzylic hydroxylationof its 3'methyl group regioselectively into twoinactive metabolites, 3'-hydroxymethylmefenamic acid andthe 3'carboxylate metabolite (via further oxidation of thebenzylic alcohol group). The parent drugs and these metabolitesare conjugated with glucuronic acid and excreted primarilyin the urine. Thus, although patients with knownliver deficiency may be given lower doses, it is contraindicatedin patients with preexisting renal dysfunction.
Common side effects associated with its use include diarrhea,drowsiness, and headache. The possibility of blood disordershas also prompted limitation of its administration to 7days. It is not recommended for children or during pregnancy.

Biochem/physiol Actions

Mefenamic acid is an analgesic and anti-inflammatory drug. It acts as a cyclooxygenase (COX) enzyme inhibitor. It is hepatoxic and implicated in liver injury. Contrarily, mefenamic acid elicits neuroprotection in in vivo ischemic stroke models by inhibiting cell toxicity induced by glutamate. Mefenamic due its inhibitory effect on prostaglandin synthesis can be used in reducing edema and ache.

Mechanism of action

Mefenamic acid inhibits both COX isoforms with some preference for COX-2 and modifies ion channels.

Clinical Use

Mefenamic acid is synthesized from o-chlorobenzoic acid and 2,3-dimethylaniline under catalytic conditions. Mefenamic acid is the only fenamic acid derivative that produces analgesia centrally and peripherally. Mefenamic acid is indicated for the short-term relief of moderate pain and for primary dysmenorrhea.

Safety

Mefenamic acid has mild anti-inflammatory properties and is used primarily as a short-term analgesic. Gastrointestinal disturbances, including possibly allergic diarrhea and potential renal toxicity, limit its use.

Synthesis

Mefenamic acid, N-(2,3-xylyl)anthranylic acid (3.2.19), is synthesized in basically the same manner, by the reaction of the potassium salt of 2-bromobenzoic acid with 2,3-dimethylaniline in the presence of copper (II) acetate [80,81].
Synthesis 2: mefenamic acid is prepared via the Jourdan – Ullmann – Goldberg synthesis utilizing either anthranilic acid and 3-bromo-1,2- dimethylbenzene or 2,3-dimethylaniline and an o-halobenzoic acid in the presence of a copper catalyst and a proton acceptor.

Metabolism

Mefenamic acid is absorbed rapidly following oral administration, with peak plasma levels being attained within 2 to 4 hours. It is highly bound to plasma proteins (78.5%) and has a plasma half-life of 2 to 4 hours. Metabolism occurs through regioselective oxidation of the 3′-methyl group and glucuronidation of mefenamic acid and its metabolites. Urinary excretion accounts for approximately 50 to 55% of an administered dose, with unchanged drug accounting for 6%, the 3′-hydroxymethyl metabolite (primarily as the glucuronide) accounting for 25%, and the remaining 20% as the dicarboxylic acid (of which 30% is the glucuronide conjugate). These metabolites are essentially inactive.

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