PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Mefenamic Acid”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources
PubMed1985

Differential effects of prostaglandin synthetase inhibitors on EEG in rat.

The effects of five nonsteriodal prostaglandin (PG) synthetase inhibitors on the electrocorticogram were studied in rats with chronically implanted supracortical electrodes. All of PG synthetase inhibitors produced high voltage activity in the electrocorticogram. However, behavior and spectral analysis of the electrocortical activity suggests that these drugs could be divided into two groups. Meclofenamic acid and mefenamic acid produced dose-related increases in excitation (to seizure) while ibuprofen, paracetamol and indomethacin produced dose-related increases in sedation.

Acetaminophen↗
PubMed1996

In vitro interaction of nonsteroidal anti-inflammatory drugs on oxidative phosphorylation of rat kidney mitochondria: respiration and ATP synthesis.

The in vitro interference of some of most important nonsteroidal anti-inflammatory drugs (NSAIDs) with the respiration of rat kidney (renal cortex) mitochondria and ATP synthesis was evaluated. Acetylsalicylic acid, diclofenac sodium, mefenamic acid, and piroxicam both uncoupled and inhibited oxidative phosphorylation in mitochondria energized with glutamate plus malate or with succinate, while dipyrone only uncoupled and paracetamol only inhibited it. The drug concentrations affecting mitochondrial respiration were in the low to middle micromolar range for diclofenac, mefenamic acid, and piroxicam, and in the low millimolar range for acetylsalicylic acid, dipyrone, and paracetamol. The pattern of inhibition, except for the paracetamol, was similar to that expressed by the respiratory chain inhibitors. NSAIDs also inhibited the rate of ATP synthesis in mitochondria energized with glutamate plus malate, as well as the phosphorylation potential of mitochondria. The IC50 values for rate of ATP synthesis, using 2 mM ADP, were about 0.1 mM for diclofenac sodium and mefenamic acid, 0.7 mM for piroxicam, and in the range of 5-8 mM for acetylsalicylic acid, dipyrone, and paracetamol. The potential for renal energetic cytotoxicity of NSAIDs is discussed considering their ability to interact with the oxidative phosphorylation in rat renal cortex mitochondria. A comparison is made with the interference of salicylate, the main metabolite of acetylsalicylic acid, and a classical uncoupler of oxidative phosphorylation.

Acetaminophen↗
PubMed2003

Tranexamic acid: a review of its use in the management of menorrhagia.

Tranexamic acid (Transamin), Cyklokapron, Exacyl, Cyklo-f) is a synthetic lysine derivative that exerts its antifibrinolytic effect by reversibly blocking lysine binding sites on plasminogen and thus preventing fibrin degradation. In a number of small clinical studies in women with idiopathic menorrhagia, tranexamic acid 2-4.5 g/day for 4-7 days reduced menstrual blood loss by 34-59% over 2-3 cycles, significantly more so than placebo, mefenamic acid, flurbiprofen, etamsylate and oral luteal phase norethisterone at clinically relevant dosages. Intrauterine administration of levonorgestrel 20 microg/day, however, produced the greatest reduction (96% after 12 months) in blood loss; 44% of patients treated with levonorgestrel developed amenorrhoea. Tranexamic acid 1.5 g three times daily for 5 days also significantly reduced menstrual blood loss in women with intrauterine contraceptive device-associated menorrhagia compared with diclofenac sodium (150 mg in three divided doses on day 1 followed by 25 mg three times daily on days 2-5) or placebo. Tranexamic acid, mefenamic acid, etamsylate, flurbiprofen or diclofenac sodium had no effect on the duration of menses in the studies that reported such data. In a large noncomparative, nonblind, quality-of-life study, 81% of women were satisfied with tranexamic acid 3-6 g/day for 3-4 days/cycle for three cycles, and 94% judged their menstrual blood loss to be 'decreased' or 'strongly decreased' compared with untreated menstruations. The most commonly reported drug-related adverse events are gastrointestinal in nature. The total incidence of nausea, vomiting, diarrhoea and dyspepsia in a double-blind study was 12% in patients who received tranexamic acid 1g four times daily for 4 days for two cycles (not significantly different to the incidence in placebo recipients). In conclusion, the oral antifibrinolytic drug tranexamic acid is an effective and well tolerated treatment for idiopathic menorrhagia. In clinical trials, tranexamic acid was more effective at reducing menstrual blood loss than mefenamic acid, flurbiprofen, etamsylate and oral luteal phase norethisterone. Although it was not as effective as intrauterine administration of levonorgestrel, the high incidence of amenorrhoea and adverse events such as intermenstrual bleeding resulting from such treatment may be unacceptable to some patients. Comparative studies of tranexamic acid with epsilon - aminocaproic acid, danazol and combined oral contraceptives, as well as long-term tolerability studies, would help to further define the place of the drug in the treatment of menorrhagia. Nevertheless, tranexamic acid may be considered as a first-line treatment for the initial management of idiopathic menorrhagia, especially for patients in whom hormonal treatment is either not recommended or not wanted.

Antifibrinolytic Agents↗
PubMed1998

Regulation of the activity of 27 pS nonselective cation channels in excised membrane patches from rat brown-fat cells.

The regulation of the activity of the approximately 30 pS nonselective cation channel (NSC channel) was studied by the patch-clamp technique in inside-out patches obtained from rat brown-fat cells. NSC channel activity was induced by excision; reduced redox state induced by dithiothreitol accelerated the kinetics in the excised state. The NSC channels were inhibited by the fenamates flufenamic acid and mefenamic acid but not by NS-1619 or SKF-96365. The channels were inhibited by purine nucleotides but not by polyamines. No evidence for protein kinase C, CaM kinase or protein kinase A activation of the NSC channel was obtained. NSC-channel activity was stimulated in a concentration-dependent manner by Ca2+ but the EC50 was very high (0.81 mM), in comparison to expected cytosolic Ca2+ levels. In the presence of ATP, even higher Ca2+ levels were necessary for comparable NSC-channel activation. The increase in Po was not associated with an increase in open-time constants. We conclude that although high Ca2+ levels can experimentally activate the NSC channel, a further mediatory step must probably be postulated in order to link alpha1-adrenergic stimulation to NSC-channel activation.

Adipose Tissue, Brown↗
PubMed1990

Mefenamic acid-induced neutropenia and renal failure in elderly females with hypothyroidism.

We report mefenamic acid-induced non-oliguric renal failure and severe neutropenia occurring simultaneously in two elderly females. The neutropenia was due to maturation arrest of the myeloid series in one patient. Both patients were also hypothyroid, but it is not clear whether this was a predisposing factor to the development of these adverse reactions. However, it would seem prudent not to use mefenamic acid in hypothyroid patients until the hypothyroidism has been corrected.

Acute Kidney Injury↗
PubMed1998

Comparative dissolution studies for mefenamic acid-polyethylene glycol solid dispersion systems and tablets.

The purpose of this study was to enhance the dissolution of mefenamic acid (MFA) through the formation of solid dispersion systems, and to compare the dissolution of the unformulated dispersions with those of formulated dispersions in tablets. Solid dispersions of MFA were prepared in polyethylene glycol 3350 (PEG) as a binary system, and PEG and Tween 20 (TW) as a ternary system by the melt method. The dispersions were characterized by dissolution, scanning electron microscopy, and powder x-ray diffraction studies. A decrease in MFA composition in the binary dispersion systems from 50 to 5% w/w resulted in a 50% increase in the dissolution rate during the period of study, and this was threefold higher than that of pure MFA. Incorporation of TW in the preparation of ternary dispersion systems resulted in a further increase in MFA dissolution. A sevenfold increase in MFA dissolution was observed when the ternary system composition was MFA/PEG/TW 4.7:93:2.3 (% w/w). Scanning electron microscopy and x-ray diffraction pictures showed an increase in size and decrease in crystallinity of the dispersions, respectively. Compression of the dispersions into tablets did not have any effect on the dissolution of the drug from the dispersions. Compression of pure MFA and Avicel PH 101, which was used as a diluent and disintegrant, resulted in a threefold increase in dissolution. However, the dissolution of the uncompressed mixture was identical to that of pure MFA. Thus, further processing of the solid dispersions into tablets did not decrease the rate of dissolution of the drug in the dispersions. This may be very important in the formulation of solid dispersions as tablets, which could lead to a reduction in the dose of practically water-insoluble drugs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

Contribution of chloride conductance increase to slow EPSC and tachykinin current in guinea-pig myenteric neurones.

1. Single electrode voltage clamp recordings were obtained from myenteric neurones of guinea-pig ileum in vitro. Slow excitatory postsynaptic currents (sEPSCs) were elicited by focal stimulation of interganglionic nerve strands in twenty-four of thirty neurones more than 30 min after impalement. In seventeen of twenty-four neurones, sEPSCs were associated with a conductance decrease and reversed polarity at -96 +/- 3 mV (near the reversal potential for potassium, EK); this response was due to inhibition of resting potassium conductance, gK. In seven of twenty-four neurones, there was either no net conductance change or a biphasic conductance change during the sEPSC; a reversal potential for peak currents could not be determined. 2. Application of senktide (3 microM), a neurokinin-3 receptor agonist, caused an inward current in forty-one of fifty-three neurones more than 30 min after impalement. In twenty of forty-one neurones, senktide-induced currents were due to inhibition of resting gK. In eleven of forty-one neurones there was either no net conductance change or a biphasic conductance change; a reversal potential for peak currents could not be determined. In ten out of forty-one neurones, senktide-induced currents were associated with a conductance increase (ginc); the estimated reversal potential was -17 +/- 3 mV. 3. Application of forskolin (1 microM) caused an inward current that occluded the decrease in gK caused by senktide and the sEPSC. In neurones in which sESPCs and senktide responses were associated with an unclear or biphasic conductance change, forskolin did not reduce the peak current and residual currents were usually associated with a ginc. 4. In neurones in which senktide-induced currents were associated with a ginc, reducing extracellular Cl- to 13 mM reduced senktide-induced currents by 79%. Reducing extracellular Na+, or adding tetraethylammonium (TEA, 50 mM), cobalt (2 mM) or picrotoxin (30 microM) did not change senktide-induced currents. The chloride transport/channel blockers niflumic acid and mefenamic acid (both at 100 microM) blocked senktide-induced currents. It was concluded that senktide increases chloride conductance (gCl). 5. Chord conductance measurements made between -70 and -90 mV during sEPSCs were used to determine the contribution of an increase in gCl to sEPSCs. These measurements indicated that the peak sEPSC is composed of a 90% decrease in gK and a 10% increase in gCl. Similar data were obtained from measurements made during senktide responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

The differentiation of NSAIDs and prostaglandin action using a mechanical visceral pain model in the rat.

In order to determine the role of peripheral prostanoids in a newly developed mechanical visceral pain model, several NSAIDs were studied. Systemic acetylsalicylic acid and mefenamic acid, in doses known to produce cyclooxygenase inhibition, produced limited or no analgesia using a duodenal distension model and a behavioral scale for assessment. In contrast, indomethacin at 1 mg/kg, a dose 1/100th of the highest dose of the above compounds, had a marked analgesic effect in the visceral pain model (32% of control response). These data suggest that a duodenal distension stimulus does not have a peripheral prostaglandin E2-mediated nociceptive mechanism. Furthermore, the results obtained with indomethacin support an alternate, possibly central nonprostanoid visceral antinociceptive action.

Acetates↗
PubMed1982

Role of prostaglandins in rat pineal neuroeffector junction. Changes in melatonin and norepinephrine release in vitro.

The effects of prostaglandins (PGs) on melatonin secretion and norepinephrine (NE) and release in rat pineal gland were examined in vitro. To study melatonin secretion, pineal explants were incubated for 6 h in tissue culture 199 medium with 1-1000 nM PGE1, PGE2, or PGF2 alpha. melatonin concentration in pineal glands and media was determined by RIA, PGE2 increased pineal and medium melatonin at all concentrations tested, with a maximum of 1 nM; PGE1 was effective only at concentrations 100-1000 times greater, whereas 100 nM PGF2 alpha gland. Exposure of pineal explants to 10 microM NE brought about a 20-fold increase in melatonin release to the medium. This effect was impaired significantly, but not blocked, by prior exposure to indomethacin, acetylsalicylic acid, or mefenamic acid at supramaximal concentrations to inhibit PG synthesis (100 microM). To examine the effects of PGs on NE release, endogenous NE stores in pineal nerve endings were labeled in vitro by incubating rat pineals with [3H]NE for 30 min. Fifty minutes later, at the time when spontaneous radioactivity efflux had leveled off, transmitter release was elicited by a 1-min exposure to 80 mM K+ (S1), and the stimulus was repeated 35 min later (S2). PGs (10-100 nM) were added to the medium 20 min before S2. Ratios between fractional release of the two consecutive stimulations (S2/S1) varied between 0.84 and 1.16 in control pineals. Only 100 nM PGE2 impaired significantly transmitter release by 40%. These results suggest that PGE2 can play a role in NE-stimulated melatonin synthesis. At greater concentrations PGE2 inhibits NE release from pineal nerve endings.

Alprostadil↗
PubMed1987

Effects of antipyretics in rinderpest virus infection in rabbits.

Administration of acetylsalicylic acid or mefenamic acid during experimental infection of rabbits with a rabbit-adapted strain of rinderpest virus did not prevent initiation of the febrile response but significantly reduced the duration of fever. Suppression of fever had a markedly deleterious effect on the course of infection, resulting in an increased content of infectious virus in the mesenteric lymph nodes, increased mortality, and retarded recovery in animals that survived the infection. Histological lesions were mainly lymphocytic depletion in lymphoid organs and lymphoid necrosis in both rabbits treated with antipyretics and those left untreated, but damage was more pronounced in the former than in the latter. More viral antigen was detected by immunofluorescence in lymphoid organs of drug-treated rabbits than in those of untreated rabbits. Antipyretic treatment resulted in higher serum interferon levels in the early phase of infection and an increased antibody response in animals that survived the infection.

Animals↗
PubMed2001

Inhibition of store-operated calcium entry contributes to the anti-proliferative effect of non-steroidal anti-inflammatory drugs in human colon cancer cells.

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit proliferation and angiogenesis in colorectal cancer. We examined a possible involvement of store-operated calcium (SOC) entry in human colon carcinoma cells (HRT-18), which require calcium for proliferation. Acetyl-salicylic-acid (ASA), mefenamic acid (MEF) and sulindac sulfide (SUS) inhibited cell proliferation with the following order of potency: SUS > MEF >> ASA. SUS but not MEF and ASA induced apoptosis following low-dose treatment. Furthermore, SUS and MEF significantly altered the cell cycle distribution. The ability of NSAIDs to inhibit SOC entry was assessed by measuring the intracellular calcium concentration ([Ca2+]i) in response to calcium store depletion using the endoplasmic calcium ATPase inhibitor thapsigargin. SUS and MEF, but not ASA significantly inhibited SOC entry. A causal link between SOC entry inhibition and anti-proliferative activity was tested using the inorganic SOC entry inhibitor La3+ and the specific organic inhibitor N-1-n-octyl-3,5-bis-(4-pyridyl)triazole (DPT). Both La3+ and DPT inhibited cell proliferation and SOC entry. Analogous to MEF, the anti-proliferative effect of DPT was mediated by cell cycle arrest and not by induction of apoptosis. These data indicate a role of SOC entry for cell proliferation in cancer cells and suggest a novel anti-proliferative NSAID mechanism in addition to its known influence on lipid metabolism.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1980

Antagonism by fenamates of prostaglandin action in guinea-pig and human alimentary muscle.

1 Low concentrations of meclofenamate, flufenamate or mefenamate had little effect on contractions in response to acetylcholine in any tissue studied. 2 Sodium meclofenamate potently antagonized contractions of guinea-pig ileum longitudinal muscle to prostaglandin E2 (PGE2), PGF2 alpha or PGD2. 3 In guinea-pig colonic longitudinal muscle, contractions to PGE2 were reduced by sodium meclofenamate, but contractions of the longitudinal or circular muscle to PGF2 alpha or PGD2 were less effectively inhibited. 4 In human gastrointestinal longitudinal muscle, sodium meclofenamate or flufenamate potently inhibited contractions to PGF2 alpha, but not to PGE2. 5 Sodium mefenamate or mefenamic acid, even in high concentrations, had little effect on contractions to PGF2 alpha, but tended to inhibit PGE2-induced contractions of human gastrointestinal longitudinal muscle. 6 The therapeutic advantages of prostaglandin synthesis inhibitors which also antagonize responses to certain prostaglandins are discussed.

Animals↗
PubMed1993

A major role for cytochrome P450TB (CYP2C subfamily) in the actions of non-steroidal antiinflammatory drugs.

Most non-steroidal antiinflammatory drugs (NSAIDs) are extensively metabolized by liver oxidation with broad interindividual variability, but little is known about the nature of the enzyme(s) catalysing these reactions. The role of specific cytochrome P450 isozymes in the formation of the major oxidized metabolites of phenylacetic acid (diclofenac), propionic acid (ibuprofen), fenamate (mefenamic acid) and oxicam (piroxicam and tenoxicam) derivatives was studied in human liver microsomes using mostly selective inhibition by known substrates and inhibitors of specific cytochrome P450 monooxygenases. A common isozyme (P450TB, CYP2C subfamily) controls the major elimination pathways of these NSAIDs. The authors have also determined, in two in vitro models of P450TB activity, the affinity for this isozyme of other NSAIDs (acetylsalicylic acid, indomethacin, pirprofen). The NSAIDs tested displayed a high affinity (5-500 microM): diclofenac approximately mefenamic acid > ibuprofen approximately indomethacin approximately piroxicam approximately tenoxicam > acetylsalicylic acid approximately pirprofen. Cytochrome P450TB therefore plays a key role in the oxidation by human liver of major NSAIDs from various chemical classes. Inhibition data and chemical structure similarities suggest that many other NSAIDs may be substrates of this isozyme as well. P450TB appears to be a common site both for the control of interindividual differences in the capacity to oxidize major NSAIDs and for interactions involving NSAIDs as well as other known substrates (oral anticoagulants, hypoglycaemic sulfonylureas, phenytoin) or inhibitors (antifungals, antibacterial sulfonamides, calcium channel blockers) of P450TB. Consequently this P450 isozyme is likely to be a major determinant of NSAIDs action.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Mefenamic acid-induced apoptosis in human liver cancer cell-lines through caspase-3 pathway.

Non-steroidal anti-inflammatory drugs (NSAIDs) have anti-proliferative effects and induce apoptosis in colon and other cancers. In the present study, we report that mefenamic acid (MEF), a member of NSAIDs, has an inhibitory effect on a proliferation of liver cancer cells. We used Chang and Huh-7 cells as human liver cancer cells. MEF-treated Huh-7 and Chang cells displayed apoptotic morphological changes and the portion of cells in sub G1 was increased 3-fold and 6-fold, respectively, at a 200 microM concentration. We also show an MEF-enhanced binding of annexin V to cells and an increased activity of caspase-3 to cleave PARP-1 and caspase itself. The inhibitor of caspase-3 blocked PARP-1 cleavage activity and protected against MEF-induced apoptotic cell death. These results indicate that MEF induces apoptosis in human liver cancer cells.

Annexin A5↗
PubMed1989

Drug competition for thyroxine binding to transthyretin (prealbumin): comparison with effects on thyroxine-binding globulin.

We examined the effect of 26 drugs on T4 binding to transthyretin (TTR; prealbumin) and T4-binding globulin (TBG) by determining their ability to inhibit [125I]T4 binding to TTR isolated from normal human plasma and to serum diluted 1:10,000, respectively. The hierarchies for drug inhibition of T4 binding differed greatly for these two proteins. Relative to T4, the drugs were much more potent inhibitors of [125I]T4 binding to TTR than to TBG. Compounds of the anthranilic acid class, such as flufenamic, meclofenamic, and mefenamic acids, interacted particularly strongly with TTR. Flufenamic acid was more potent than T4 itself in inhibiting [125I]T4 binding [175 +/- 17% (+/- SD); cf. T4; n = 3; P less than 0.001], while mefenamic acid, diflunisal, and meclofenamic acid were 20-26% as potent as T4 in their interaction with TTR. The reactivity of diclofenac, fenclofenac, indomethacin, sulindac, and the diuretic ethacrynic acid was 0.8-2.1% relative to that of T4. In contrast, furosemide, the drug most highly reactive with TBG, was only 0.11 +/- 0.03% (n = 7) as potent as T4, followed by meclofenamic acid greater than mefenamic acid greater than fenclofenac greater than flufenamic acid greater than diflunisal greater than milrinone. Aspirin and sodium salicylate were, respectively, 0.05% and 0.20% as active as unlabeled T4 as inhibitors of [125I]T4 binding to TTR, but these compounds had only 3-4 x 10(-6)% of the activity of T4 for TBG binding. Diphenylhydantoin had no detectable effect on T4 binding to TTR and was 2.9 x 10(-4)% as reactive as T4 with TBG. Amiodarone did not interact with either binding site. Drug interactions with TTR may be important when this protein becomes a major circulating T4-binding protein, as in patients with complete or partial TBG deficiency, or when serum T4 is markedly elevated. Such interactions may also be important where TTR is the dominant tissue T4-binding protein, as in the choroid plexus. In addition, the drug competitors described here may be useful as probes to further define the structural basis for specific ligand interactions with different classes of T4-binding sites.

Binding Sites↗
PubMed2002

Characterization of mefenamic acid-guaiacol ester: stability and transport across Caco-2 cell monolayers.

PURPOSE: Prodrug of non-steroidal anti-inflammatory drugs (NSAIDs) or NSAIDs linked with guaiacol have been reported to suppress gastrointestinal (GI) toxicity or induce GI protective effect. In this study. mefenamic-guaiacol ester was synthesized and its physicochemical properties. stability, and transport across Caco-2 monolayers were investigated. METHODS: Synthesis of the ester was carried out using mefenamic acid, guaiacol. N. N'-dimethylaminopyridine, and N,N'dicyclohexylcarbodiimide. The hydrolysis of the ester was investigated in aqueous buffer solutions pH 1-12 as well as in Caco-2 homogenate, human plasma, and porcine liver esterase. Caco-2 cell monolayers were utilized for transport studies. Due to the high lipophilicity of the ester with a calculated logP of 6.15, bovine serum albumin (BSA, 4%) was included in the receiver compartment to obtain a good in vitro-in vivo correlation. Permeation of the ester was assessed with or without the exposure of cells to PMSF, an inhibitor of esterase. RESULTS: The ester was stable at a wide pH range from 1-10. However, it was hydrolyzed by enzymes from porcine liver esterase and Caco-2 homogenate. With the PMSF exposure on the apical (AP) side and in the presence of 4% BSA on the basolateral (BL) side, the transported amount of the ester from AP-to-BL direction was 14.63% after 3 hr with a lag time of 23 min. The Papp for the ester was 4.72 x 10(-6) cm s(-1). CONCLUSION: The results from hydrolysis studies indicate that this ester is a prodrug. The Papp value suggests the moderate absorption characteristic of the compound. The accumulation of this highly lipophilic ester in Caco-2 cells is reduced in the presence of BSA.

Animals↗
PubMed1978

Trial of prostaglandin-synthetase inhibitors in primary dysmenorrhoea.

The prostaglandin-synthetase inhibitors, mefenamic acid and flufenamic acid, were compared with the analgesic, dextropropoxyphene/paracetamol, in the treatment of primary dysmenorrhoea in a double-blind crossover trial. Results were assessed in 30 patients who took each drug during menstruation for three consecutive cycles. The patients' assessment of each drug suggests that both mefenamic acid and flufenamic acid are more effective than the other analgesic for general relief of symptoms and for most of nine individual symptoms subjectively assessed by the patient. There was less absenteeism from work or school during mefenamic-acid treatment and fewer capsules of mefenamic acid were taken compared with the other two drugs. Patients took significantly fewer additional analgesics during mefenamic-acid therapy than during treatment with the other two drugs. 5 patients had possible side-effects--3 patients on mefenamic acid and 2 on dextropropoxyphene/paracetamol.

Acetaminophen↗