Disease relevance of mefenamic acid

• Mefenamic acid for dysmenorrhea [1].
• Non-oliguric renal failure developed in six elderly women who had been prescribed 1--2 g of mefenamic acid daily for 2--6 weeks for the relief of musculoskeletal pain [2].
• Mefenamic acid overdose mimicking brainstem stroke [3].
• Alpha-methyldopa-type autoimmune hemolytic anemia caused by lobenzarit disodium of a mefenamic acid derivative and immunomodulator [4].
• A patient with acute interstitial nephritis secondary to ingestion of a Chinese herbal medicine adulterated with mefenamic acid is presented [5].

Psychiatry related information on mefenamic acid

• Moreover, our study demonstrates for the first time that mefenamic acid improves learning and memory impairment in an Abeta(1-42)-infused Alzheimer's disease rat model [6].
• Mefenamic acid prevents assessment of drug abuse with EMIT assays [7].
• An elderly patient with bipolar manic-depressive psychosis, stabilised satisfactorily on lithium carbonate, developed acute symptoms of lithium toxicity shortly after commencing mefenamic acid [8].
• Ibuprofen, sulindac, mefenamic acid, and low dose meclofenamic acid increased the latency-to-onset in the flurothyl and/or PTZ models; the electroshock, picrotoxin and bicuculline models were not significantly affected by any of the pretreatment agents [9].

High impact information on mefenamic acid

• Indomethacin or mefenamic acid, two structurally different prostaglandin synthesis inhibitors, markedly inhibited the degree of vasodilation induced by rTNF in the three arteriolar orders [10].
• Coma in mefenamic acid poisoning [11].
• Avoidance of mefenamic acid in epilepsy [12].
• Aspirin, mefenamic acid, and ibuprofen administration resulted in marked (45% to 80%) improvement in forced expiratory volume in 1 second (FEV1) compared to lactose placebo [13].
• Drugs that precipitate possibly life-threatening bronchoconstriction and are absolutely contraindicated in patients with aspirin-induced asthma include indomethacin, mefenamic acid, flufenamic and meclofenamic acids, ibuprofen, fenoprofen, ketoprofen, naproxen, diclofenac, amidopyrine, noramidopyrine, phenylbutazone, flumizole, and ditazol [14].

Chemical compound and disease context of mefenamic acid

• Lithium toxicity and mefenamic acid. A possible interaction and the role of prostaglandin inhibition [8].
• The efficacy and safety of nimesulide suspension were evaluated in comparison with mefenamic acid in a double-blind multicentre study that recruited 100 children with acute respiratory tract infections [15].
• The nonsteroidal anti-inflammatory drugs (NSAID) indomethacin and mefenamic acid, at concentrations ranging from 3 microM to 18 microM, enhanced antigen-induced slow reacting substance of anaphylaxis (SRS-A) release from sensitized fragmented guinea-pig lung [16].
• Forty ambulant migraine patients were supplied with oral medication for six consecutive attacks; metoclopramide 10 mg was administered in all attacks, and paracetamol 500 mg and mefenamic acid 500 mg for three attacks each [17].
• Tranexamic acid and mefenamic acid are among the most effective first-line drugs used to treat menorrhagia [18].

Biological context of mefenamic acid

• MMPT was estimated by the extent of mitochondrial swelling induced by 10 microM CaCl2 plus 1.5 mM inorganic phosphate or 30 microM mefenamic acid [19].
• Acetyl-salicylic-acid (ASA), mefenamic acid (MEF) and sulindac sulfide (SUS) inhibited cell proliferation with the following order of potency: SUS > MEF >> ASA [20].
• Body temperature returned to normal on the third day for most of the nimesulide-treated patients, but only on the fifth day for the mefenamic acid group [15].
• Half-maximal inhibition was about 10 microM for flufenamic acid and mefenamic acid, whereas niflumic acid was less potent (IC50 about 50 microM) [21].
• These results indicate that mefenamic acid increased voltage-dependent nifedipine-sensitive inward Ba2+ currents through the activation of L-type Ca2+ channels with different kinetics from those of Bay K 8644 in pig urethral myocytes [22].

Anatomical context of mefenamic acid

• Although mefenamic acid has many of the pharmacologic and physicochemical properties of aspirin and produces gastrointestinal ulceration in animals when administered in large doses, the English literature reveals only one case of gastric ulceration and a single instance of upper-gastrointestinal tract hemorrhage associated with its use [23].
• A 46-year-old woman developed hematemesis and melena two weeks after starting mefenamic acid therapy for osteoarthritis of the spine [23].
• We also show that mefenamic acid decreases the production of the free radical nitric oxide and reduces cytochrome c release from mitochondria induced by Abeta(1-42), Swe-APP, or APP-CTs in neuronal cells [6].
• Niflumic acid, mefenamic acid, flufenamic acid, and 4,4'-diisothiocyanatostilbene-2,2'- disulfonic acid, which are commonly used in Xenopus oocytes to suppress endogenous Ca(2+)-activated Cl- channels, were tested for their effects on IsK channels [24].
• These results indicate that mefenamic acid increases the channel activities of two distinct types of K+ channels (i.e. BKCa channels and KATP channels) and decreased 4-AP-sensitive K+ channels in pig urethral myocytes [25].

Associations of mefenamic acid with other chemical compounds

• Sprague-Dawley rats were divided into four groups and gavage fed either vehicle suspension (control), mefenamic acid, mefenamic acid+caffeine or caffeine only for 4 months [26].
• Acetaminophen, N-acetylcysteine, propylthiouracil, D-penicillamine, mefenamic acid, dapsone, and methimazole all inhibited MPO at clinically achievable concentrations [27].
• Treatment with mefenamic acid (10 micrograms/ml), a prostaglandin synthesis inhibitor, produced marked constriction of arterioles but not of venules, suggesting the involvement of endogenous vasodilator prostaglandins in the regulation of resting diameters of arterioles [28].
• The presence of mefenamic acid results in a reduced extracellular space size, whereas cellular water content was increased by both mefenamic acid and acetylsalicylic acid [29].
• Therefore, an additional constriction was found when MA was administered after l-NNA in the presence of the thromboxane A2 synthase-PGH2 (TP) receptor antagonist SQ-29548 [30].

Gene context of mefenamic acid

• Mefenamic acid is therefore a potent and selective inhibitor of human liver SULT1A1 [31].
• The competitive inhibitor of hCOX-1, mefenamic acid, also displayed competitive inhibition of hCOX-2 [32].
• The KCNQ1/KCNE1/KCNE2 current had a more depolarized activation voltage, a faster deactivation kinetics, and a less sensitivity to activation by mefenamic acid [33].
• Here we report that both native ETA receptors in vascular smooth-muscle cells and recombinant ET(A) receptors expressed in mouse fibroblasts (Ltk cells) are functionally coupled with a non-selective cation channel, which is permeable to Ca2+ and is blocked by mefenamic acid [34].
• In the presence of superoxide dismutase and catalase, l-NNA-induced vasoconstriction is reduced, and the dilation observed after addition of MA in presence of the reactive oxygen species is no longer present [30].

Analytical, diagnostic and therapeutic context of mefenamic acid

• Mefenamic acid for dysmenorrhea in patients with intrauterine devices [35].
• Effects of mefenamic acid on placental deiodination were examined by HPLC [36].
• We found that l-NNA after MA induced an additional constriction, whereas MA after l-NNA induced a relative dilation [30].
• Although in the presence of multiple drug therapy the causative agent cannot be identified with absolute certainty, the association of these severe idiosyncratic hepatic and dermatological reactions with haemolytic anaemia strongly suggests mefenamic acid as the most likely culprit [37].
• 3. L-NAME and L-NOARG (100 microM) had no effect on the basal perfusion pressures in tissues from either WKY or SHRs, and mefenamic acid only induced a significant reduction of the basal perfusion pressures in the venous mesenteric vessels isolated from WKY [38].

References