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.

1,090 records · Page 61Linked to original sources

PubMed1983

[A new nitrogen-containing polycyclic system. Synthesis and pharmacologic properties of benzofuran and thienothiadiazolepyrimidine derivatives. I].

A series of 5H-benzofuro[3,2-d]1,3,4-thiadiazolo[3,2-a]-pyrimidin-5-ones and 1,3,4-thiadiazolo[3,2-a]thieno[2,3-d]pyrimidin-5-ones were synthesized and their analgesic, antiinflammatory, antiexudative and ulcerogenic activities were evaluated. The analgesic and antiexudative activities of several derivatives proved to be less than that of indomethacin and much higher than that of mefenamic and acetylsalicylic acids. Acute toxicity and ulcerogenic effects were significantly lower than those of reference drugs.

Animals↗

PubMed1981

[Pharmacologic studies on Ro 12-0068, a new non-steroidal anti-inflammatory drug (author's transl)].

The pharmacological profile of Ro 12-0068 as a new anti-inflammatory agent has been established in 9 different animal models and was compared with the profiles of 10 reference drugs. In adjuvant arthritis, scald-related edema and bradykinin-induced capillary permeability tests, the inhibitory potency of Ro 12-0068 was greater than findings in the case of diclofenac sodium which was the most potent agent available, while Ro 12-0068 exerted a stronger inhibitory effect on granuloma formation than did indomethacin. Anti-inflammatory potency of Ro 12-0068 in other models was equivalent to that of piroxicam. Ro 12-0068 was categorized as a potent anti-inflammatory agent and was grouped with diclofenac sodium, indomethacin and piroxicam, as compared to rather weak agents such as naproxen, carprofen, phenylbutazone, flufenamic, mefenamic, and acetylsalicylic acids. In fasting rats, ulcerogenicity of Ro 12-0068 in the gastric glandular and duodenal portions was weaker than that of indomethacin, appeared to be less than that of piroxicam and was equivalent to that of diclofenac sodium. Induction of fecal occult bleeding in dogs was markedly greater in case of indomethacin and piroxicam than with Ro 12-0068, within few days after oral treatment. Ro 12-0068 and piroxicam had much the same inhibitory effect on prostaglandin synthesis of inflammatory tissues and exudates from gastro-intestinal tissues. Nevertheless, therapeutic indices of Ro 12-0068 in rats were larger than those of piroxicam, in all models, and those of indomethacin in most cases. These results strongly suggest that Ro 12-0068 is a potent anti-inflammatory agent and that the occurrences of related gastro-intestinal disturbances are fewer.

Analgesics↗

PubMed1995

Action of diphenylamine carboxylate derivatives, a family of non-steroidal anti-inflammatory drugs, on [Ca2+]i and Ca(2+)-activated channels in neurons.

Ca(2+)-activated channels, including Ca(2+)-activated non-selective (CAN) channels and Ca(2+)-activated Cl- channels play important roles in regulating the electrical activity of neurons. No blockers of neuronal CAN channels have been previously reported. We used 2-electrode voltage clamping to measure membrane currents and fura-2 fluorescence imaging to measure [Ca2+]i in molluscan neurons. We show that the diphenylamine carboxylate derivative flufenamate (FFA), but not mefenamate or the parent compound, cause a transient increase in ICAN and a slow outward current, and a maintained increase in [Ca2+]i. We interpret this as a FFA-dependent release of Ca2+ from intracellular stores and Ca2+ influx, [Ca2+]i-dependent activation of the CAN and slow outward currents, and slow FFA-dependent channel block.

Animals↗

PubMed1994

Differential microvascular response to cyclooxygenase blockade in the rat small intestine during acute bacteremia.

To determine whether arachidonic acid metabolites are mediators of regional blood flow changes during sepsis, we examined the effects of cyclooxygenase blockade on intestinal microvascular diameters and blood flow during acute bacteremia, induced in the rat by the intravenous injection of 10(9) live Escherichia coli. Mean arterial pressure, cardiac output, intestinal microvascular diameters, and blood flow were measured in the presence or absence of a topically applied selective cyclooxygenase inhibitor (mefenamate). Bacteremia caused a diffuse constriction of both arterioles and venules and a concomitant 50% decrease in blood flow. Treatment with mefenamate did not affect baseline intestinal microvascular tone or bacteremia-induced arteriolar constriction and hypoperfusion, but did reverse an intense venular constriction. Our results suggest that the small intestinal microcirculation has a differential response to cyclooxygenase products of arachidonic acid metabolism during acute bacteremia. They appear not to be mediators of the intestinal arteriolar constriction and hypoperfusion observed during acute E. coli bacteremia, but profoundly influence the mesenteric venular constriction. These observations support the concept that microvascular control mechanisms are different not only between but within organ specific vascular beds.

Animals↗

PubMed2003

Salicylate induces tinnitus through activation of cochlear NMDA receptors.

Salicylate, the active component of aspirin, is known to induce tinnitus. However, the site and the mechanism of generation of tinnitus induced by salicylate remains unclear. Here, we developed a behavioral procedure to measure tinnitus in rats. The behavioral model was based on an active avoidance paradigm in which rats had to display a motor task (i.e., to jump on a climbing pole when hearing a sound). Giving salicylate led to a decrease in the percentage of correct responses (score) and a drastic increase in the number of false positive responses (i.e., animals execute the motor task during a silent period). Presentation of the sound at a constant perceptive level prevents decrease of the score, leading to the proposal that score is related to hearing performance. In contrast, the increase of false positive responses remained unchanged. In fact, animals behaved as if they hear a sound, indicating that they are experiencing tinnitus. Mefenamate in place of salicylate also increased the number of false positive responses, suggesting that salicylate-induced tinnitus is related to an inhibition of cyclooxygenase. One physiological basis of salicylate ototoxicity is likely to originate from altered arachidonic acid metabolism. Because arachidonic acid potentiates NMDA receptor currents, we tested the involvement of cochlear NMDA receptors in the occurrence of tinnitus. Application of NMDA antagonists into the perilymphatic fluids of the cochlea blocked the increase in pole-jumping behavior induced by salicylate, suggesting that salicylate induces tinnitus through activation of cochlear NMDA receptors.

Action Potentials↗

PubMed1991

Development of affinity labeling agents based on nonsteroidal anti-inflammatory drugs: labeling of the nonsteroidal anti-inflammatory drug binding site of 3 alpha-hydroxysteroid dehydrogenase.

Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their effect by inhibiting the target enzyme cyclooxygenase (prostaglandin H2 synthase); however, little is known about the peptides comprising its NSAID binding site. Hydroxyprostaglandin dehydrogenases also bind NSAIDs, but their NSAID binding sites have not been well characterized. Using existing synthetic strategies, we have incorporated the bromoacetoxy affinity labeling moiety around the perimeter of two potent NSAIDs, indomethacin and mefenamate, a N-phenylanthranilate. The compounds synthesized were 1-(4-(bromoacetamido)benzyl)-5-methoxy-2-methylindole-3-acetic acid (1), 3-(2-(2-bromoacetoxy)ethyl)-1-(4-chlorobenzyl)-5-methoxy-2-methylindole (2), 4-(bromoacetamido)-N-(2,3-dimethylphenyl)anthranilic acid (3), N-(3-(bromoacetamido)phenyl)-anthranilic acid (4), and N-(4-(bromoacetamido)phenyl)anthranilic acid (5). To access whether these compounds have general utility in labeling NSAID binding sites, the compounds were evaluated as affinity labeling agents for 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) from rat liver cytosol. This enzyme displays 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase activity, is inhibited potently by NSAIDs, and is homologous to bovine lung prostaglandin F synthase. Compounds 1-5 were shown to affinity label the NSAID binding site of 3 alpha-HSD. They inactivated 3 alpha-HSD through an E.I complex in a time- and concentration-dependent manner with t1/2 values ranging from seconds to hours. Ligands that compete for the active site of 3 alpha-HSD (NAD+ and indomethacin) afforded protection against inactivation, and the inactivators could demonstrate competitive kinetics against 3 alpha-hydroxysteroid substrates by forming an E.NAD+.I complex.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗

PubMed2006

General trends in the desolvation behavior of calcium salts.

PURPOSE: This paper is concerned with the solid-state characterization of dehydrated calcium salts as well as the effect of dehydration on the physical properties of these salts. METHODS: The salts were analyzed by X-ray powder diffraction (XRPD), single crystal X-ray and polarized light microscopy (PLM). RESULTS: Our research was able to identify three general behaviors of the desolvation of calcium salts of carboxylic acids. Upon desolvation, ethanolate and pentahydrate calcium indomethacin (CaIndo and CaInd2, respectively) stayed crystalline, fenoprofen calcium (CaFEN), calcium ketoprofen (CaKTN), calcium salicylate (CaSAL), calcium mefenamate (CaMEF) and calcium tolfenamate (CaTOLF) became mesophases, while calcium diflunisal became partially crystalline. On the other hand, the solubility studies of CaFEN, CaKTN and CaSAL showed that all dehydrated calcium salts had higher solubility than their crystalline counterparts and amorphous CaKTN had higher solubility than mesomorphous CaKTN. CONCLUSIONS: Several factors influence the desolvation behavior of calcium salts. We believe the flexibility of the benzene rings in CaKTN, CaFEN, CaMEF and CaTOLF was important for these products to become mesomorphous when they loose their crystalline water; meanwhile, CaDIF where the two benzene rings are coplanar remained crystalline when heated. Additionally, the existence of water channels and the hydrogen bonding networks in the crystals is hypothesized to play an important role in the desolvation behavior of these materials.

Calcium↗

PubMed1996

Volume-sensitive taurine efflux from mammary tissue is not obliged to utilize volume-activated anion channels.

Cell-swelling, induced by a hyposmotic shock, activates the release of taurine from lactating rat mammary tissue explants. The degree of stimulation of taurine efflux was dependent upon the extent of cell-swelling. Volume-sensitive taurine release was attenuated by the anion transport inhibitors NPPB, DIOA, DIDS, niflumate, flufenamate, mefenamate and diiodosalicylate but not by salicylate. Cell-swelling, following a hyposmotic challenge, did not increase the unidirectional efflux of radiolabelled I- or D-asparate from mammary tissue explants. The results suggest that although mammary tissue expresses a volume-sensitive amino acid transport system which is inhibited by anion transport blockers the pathway has no identity with volume-activated anion channels.

Animals↗

PubMed1982

Hypoglycemic action of 2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenylethyl]pyridine dihydrochloride sesquihydrate (DG-5128), a new hypoglycemic agent.

2-[2-(4,5-Dihydro-1H-imidazol-2-yl)-1-phenylethyl]pyridine dihydrochloride sesquihydrate (GD-5128) is a new hypoglycemic agent structurally unrelated to the known hypoglycemics. It was effective in reducing fasting blood glucose levels in mice, rats, dogs and monkeys at a single oral dose ranging from 5 to 25 mg/kg. DG-5128 was also effective in suppressing hyperglycemia induced by oral and subcutaneous glucose load in mice, rats and monkeys. In addition, it was interesting to find that DG-5128 effectively suppressed glucose-induced and post-prandial hyperglycemia in genetically diabetic mice of AyKK strain which were resistant to the action of tolbutamide, and that it strongly and specifically inhibited adrenaline-induced platelet aggregation. The hypoglycemic activity was not affected by simultaneous administration of other drugs including mefenamate, sulfamonomethoxine, cefazolin, dicoumarol, furosemide and clofibrate. DG-5128 did not cause lactic acidosis in rats even after repeated administration of large doses. These findings suggest usefulness of DG-5128 as a new anti-diabetic agent.

Animals↗

PubMed1989

Prostanoids in regulation of postprandial jejunal hyperemia and oxygen uptake.

The role of prostanoids in regulation of jejunal blood flow (JBF) was studied in anesthetized dogs. Intra-arterial infusions of arachidonate produced biphasic changes and dose-dependent decreases in jejunal vascular resistance (JVR) in untreated and aspirin-pretreated dogs, respectively; mefenamate abolished these responses. The jejunum released prostaglandin I2 (PGI2) greater than PGE2 greater than thromboxane A2 (TXA2) (radioimmunoassay) under resting conditions, and food enhanced the release of PGE2 greater than PGI2 greater than TXA2 greater than PGF2 alpha. Addition of arachidonate to food enhanced TXA2 and PGF2 alpha releases and decreased PGI2 and PGE2 releases, while inhibiting the food-induced increases in JBF and O2 uptake; mefenamate inhibited these arachidonate actions. A TXA2 receptor antagonist (SQ-29548) reversed the arachidonate vascular and metabolic actions. Intra-arterial infusions of PGI2 or PGE2 decreased, whereas TXA2 analogue U-44069 or PGF2 alpha increased JVR. A mixture of these prostanoids infused at blood concentrations similar to the increase observed during food placement did not alter JVR. At concentrations similar to the increases observed when arachidonate was added to luminal food, the infusions increased JVR and abolished the food-induced decrease in JVR. In conclusion, jejunal productions of PGI2, PGE2, TXA2, and PGF2 alpha increase during nutrient absorption. Addition of arachidonate to food attenuates the former two and enhances the latter two releases, which act to attenuate food-induced jejunal hyperemia.

Animals↗