Mefenamic acid

Structural formula
General
Non-proprietary name	Mefenamic acid
other names	2- (2,3-Dimethylphenylamino) benzoic acid ( IUPAC ) ; Acidum mefenamicum ( Latin ) ;
Molecular formula	C 15 H 15 NO 2
Brief description	white to almost white, microcrystalline, polymorphic powder
External identifiers / databases
EC number	200-513-1
ECHA InfoCard	100,000,467
PubChem	4044
ChemSpider	3904
DrugBank	DB00784
Wikidata	Q284321
Drug information
ATC code	M01 AG01
Drug class	Nonsteroidal anti-inflammatory drugs
Mechanism of action	Prostaglandin synthesis inhibitors
properties
Molar mass	241.29 g · mol -1
Physical state	firmly
Melting point	230-231 ° C
pK s value	4.2
solubility	practically insoluble in water (20 mg · l −1 at 30 ° C), sparingly soluble in dichloromethane and ethanol , soluble in dilute alkali hydroxide solutions
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302
	P: no P-phrases
Toxicological data	740 mg kg −1 ( LD 50 , rat , oral ) ; 112 mg kg −1 ( LD 50 , rat , iv ) ; 525 mg kg −1 ( LD 50 , mouse , oral ) ; 96 mg kg −1 ( LD 50 , mouse , iv ) ; 120 mg kg −1 ( LD 50 , mouse , ip ) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Mefenamic acid is a non-steroidal anti-inflammatory drug . It inhibits the formation of prostaglandins (messenger substances) and thus has an analgesic, anti-inflammatory and fever-lowering effect. Mefenamic acid is broken down in the liver and excreted in the urine and stool. Mefenamic acid was patented by Parke-Davis in 1961 . In contrast to Austria or Switzerland, where mefenamic acid is often used as a pain reliever, the active ingredient is not approved in Germany (as of January 2017).

Presentation and extraction

Mefenamic acid is synthesized by coupling 2,3-dimethylaniline with the potassium salt of 2-bromobenzoic acid in the presence of copper acetate .

properties

Mefenamic acid belongs to the group of anthranilic acid derivatives , which also includes flufenamic acid , tolfenamic acid and meclofenamic acid . Anthranilic acid derivatives are also known as fenamates. The chemical name is 2 - [(2,3-dimethylphenyl) amino] benzoic acid. Mefenamic acid, like all antipyretic anti-inflammatory drugs, is a weak acid. Two polymorphic forms of the compound with melting points 227-230 ° C (form I) and 215-220 ° C (form II) are known. Both forms form an enantiotropic system with a transition point at 130 ± 10 ° C. Below this temperature and thus at room temperature, Form II is the thermodynamically stable form and Form I is metastable. The relationship is reversed above the transition point. Form I becomes stable and Form II becomes metastable.

application areas

Areas of application are acute and chronic pain in rheumatic diseases, muscle pain, pain in the spinal column (intervertebral disc discomfort), pain, swelling and inflammation after injuries or operations, pain in primary dysmenorrhea (menstrual pain), to reduce menstrual bleeding (hypermenorrhea). According to Pfizer, mefenamic acid should not be used during pregnancy and breastfeeding.

Side effects

Common : diarrhea, usually dose-dependent, in which case the dose should be reduced. Nausea, vomiting, abdominal pain.

Rare : drowsiness, tiredness, dizziness, hypersensitivity reactions of the skin and respiratory tract, kidney dysfunction, visual disturbances, ringing in the ears.

Cramps can occur even at a relatively low dose, but they are mostly benign. In this case, benzodiazepines, such as diazepam , can be used as therapeutic agents.

Interactions

Interactions are known with the following substances: anticoagulants, corticoids, methotrexate, lithium, antidiabetic drugs, diuretics, omeprazole.

literature

Ernst Mutschler et al .: Mutschler - drug effects textbook of pharmacology and toxicology . 9th edition. Scientific Verlagsgesellschaft, Stuttgart 2008, ISBN 978-3-8047-1952-1 .

Trade names

Monopreparations

Ponstan (CH), Mephadolor (CH), Spiralgin (CH), Parkemed (A), Sportusal tabs (CH), numerous generics (A, CH) such as. B. Mefenacid (CH), Mefenam (A)

Web links

Entry on mefenamic acid at Vetpharm, accessed December 3, 2011.

Individual evidence

↑ ^a ^b European Pharmacopoeia Commission (ed.): EUROPEAN PHARMACOPOE 5TH EDITION . tape 5.0-5.8 , 2006.

↑ ^a ^b ^c ^d ^e Entry on mefenamic acid in the ChemIDplus database of the United States National Library of Medicine (NLM) .

↑ ^a ^b Mefenamic acid data sheet from Sigma-Aldrich , accessed on April 9, 2011 ( PDF ).

↑ ^a ^b ^c ^d A. Kleemann , J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications , 4th edition (2001) Thieme-Verlag Stuttgart, ISBN 978-1-58890-031- 9 .

↑ ^a ^b Burger, A .; Ramberger, R .: Thermodynamic Relationships between Polymorphic Modifications: Flufenamic Acid and Mefenamic Acid in Microchim. Acta 73 (1980) 17-28, doi : 10.1007 / BF01197228 .

↑ scientific information on Ponstan ^® in drug compendium ^® in Switzerland .

[Ph._Eur._5-1] European Pharmacopoeia Commission (ed.): EUROPEAN PHARMACOPOE 5TH EDITION . tape 5.0-5.8 , 2006.

[ChemIDplus-2] Entry on mefenamic acid in the ChemIDplus database of the United States National Library of Medicine (NLM) .