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PubMed1983

Structure-activity relationships in a series of anti-inflammatory N-arylanthranilic acids.

A large series of N-arylanthranilic acids has been prepared. Many of these compounds show high anti-inflammatory activity as measured by the anti-UV-erythema test. From this series have come the clinically useful non-steroidal anti-inflammatory agents, flufenamic acid (Arlef), mefenamic acid (Ponstel), and the latest and most potent agent, N-(2,6-dichloro-m-tolyl)anthranilic acid (meclofenamic acid, Meclomen = the sodium salt). The structure-activity relationships of this series is discussed and a graphical representation is presented which allows the prediction of activity of new agents.

Animals↗
PubMed2007

Inhibitory potential of nonsteroidal anti-inflammatory drugs on UDP-glucuronosyltransferase 2B7 in human liver microsomes.

OBJECTIVE: A number of nonsteroidal anti-inflammatory drugs (NSAIDs) are subject to glucuronidation in humans, and UDP-glucuronosyltransferase (UGT) 2B7 is involved in the glucuronidation of many NSAIDs. The objective of this study was to identify a NSAID with potent inhibitory potential against UGT2B7 using liquid chromatography with tandem mass spectrometry (LC-MS/MS). METHODS: A rapid screening method for detecting the inhibitory potential of various drugs against UGT2B7 was established using a LC-MS/MS system. The effects of nine NSAIDs (acetaminophen, diclofenac, diflunisal, indomethacin, ketoprofen, mefenamic acid, naproxen, niflumic acid, and salicylic acid) against UGT2B7-catalyzed 3'-azido-3'-deoxythymidine glucuronidation (AZTG) were investigated in human liver microsomes (HLM) and recombinant human UGT2B7. RESULTS: Mefenamic acid inhibited AZTG most potently, with an IC(50) value of 0.3 microM, and its inhibition type was not competitive. The IC(50) values for diclofenac, diflunisal, indomethacin, ketoprofen, naproxen, and niflumic acid against AZTG were 6.8, 178, 51, 40, 23, and 83 microM, respectively, while those for acetaminophen and salicylic acid were >100 microM. The IC(50) values for NSAIDs against AZTG in recombinant human UGT2B7 were similar to those obtained in HLM. CONCLUSION: The method established in this study is useful for identifying drugs with inhibitory potential against human UGT2B7. Among the nine NSAIDs investigated, mefenamic acid had the strongest inhibitory effect on UGT2B7-catalyzed AZTG in HLM. Thus, caution might be exercised when mefenamic acid is coadministered with drugs possessing UGT2B7 as a main elimination pathway.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1981

Comparative study of fluproquazone in the management of post-operative pain.

41 patients suffering from moderate to severe pain were included in a multicentric double-blind study comparing 100 mg 4-(p-fluorophenyl)-1-isopropyl-7-methyl-2(1H)-quinazolinone (fluproquazone) to 250 mg mefenamic acid during a three-day period. Both medications produced a clinically highly relevant analgesic effect in the patient population considered. Fluproquazone appears to be significantly more effective than mefenamic acid after the first dose as well as after 6-h period. Fluproquazone was better tolerated than mefenamic acid: one and four patients, respectively, experienced side-effects in the two treatment groups. These results indicate a significantly better therapeutic profile for fluproquazone as compared to mefenamic acid in the management of post-operative pain.

Adolescent↗
PubMed1986

Induction of hemolytic anemia by nonsteroidal antiinflammatory drugs.

The incidence of immune hemolytic anemia (IHA) is increasing. The proliferation of pharmaceuticals is a contributing factor to this increase. IHA is an uncommon, though significant, adverse effect of a wide variety of drugs. Several recent case reports have implicated the nonsteroidal antiinflammatory drugs (NSAIDs). Because of the extensive use of this class of drugs, a review of case reports, clinical studies, and in vitro research was conducted on NSAID-induced IHA. Mefenamic acid, ibuprofen, sulindac, naproxen, tolmetin, feprazone, and aspirin are reported to cause IHA, with mefenamic acid most frequently implicated. Mefenamic acid appears to cause hemolytic anemia by an autoimmune mechanism similar to methyldopa and aspirin by an immune complex mechanism. However, there is insufficient information concerning ibuprofen, sulindac, naproxen, tolmetin, and feprazone to assign specific mechanisms of immune hemolysis. In individuals with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, aspirin at usual therapeutic doses is not a predisposing factor to hemolysis unless other risk factors are present. Although individuals with G-6-PD deficiency are at increased risk of developing hemolytic anemia when exposed to oxidizing stresses, the use of NSAIDs does not appear to increase this risk significantly. Because NSAID-induced IHA occurs infrequently and the sensitivity of currently used tests to detect drug-dependent antibodies is limited, routine serologic testing in patients receiving NSAIDs is not justified. If hemolytic anemia occurs in a NSAID-treated patient and the history is consistent with a drug-induced etiology, the NSAID should be discontinued. With discontinuation of the offending agent, the prognosis is good. There is a rapid hematologic recovery, with a slow resolution of abnormal serologic findings.

Anemia, Hemolytic, Autoimmune↗
PubMed1997

Physiological role of Ca2+-permeable nonselective cation channel in endothelin-1-induced contraction of rabbit aorta.

We previously showed a role for a nonselective cation channel (NSCC) in the ETA-dependent action of endothelin-1 in mouse fibroblast and rabbit aortic smooth-muscle cell. To clarify the physiological significance of NSCCs in endothelin-1 (ET-1)-induced vasocontraction, we examined the effects of NSCC blockers such as mefenamic acid and SK&F 96365 on the contractions of deendothelialized rabbit aortic rings induced by a low (10[-10] M) or high (10[-8] M) concentration of ET-1. Mefenamic acid (< or =10[-3] M) had little effect on the contraction induced by 45 x 10(-3) M K+ or 1 x 10(-6) M Bay K-8644 in combination with 15 x 10(-3) M K+, indicating that it does not affect voltage-operated calcium channels (VOCs) and contractile mechanisms. The contraction by a low concentration of ET-1 was abolished after removal of extracellular Ca2+, but it was reduced only to 50% by a maximally effective concentration (10[-5] M) of nifedipine, an inhibitor of L-type VOCs (L-VOC). Mefenamic acid and SK&F 96365 inhibited the ET-1-induced contraction with 50% inhibitory concentration (IC50) values of 10(-4) M and 2 x 10(-5) M, respectively, and abolished it at 10(-3) M and 10(-4) M. By contrast, nifedipine, mefenamic acid, or SK&F 96365 had little effect on the contraction by a high concentration of ET-1. The contraction induced by a low or high concentration of ET-1 was abolished by an ETA antagonist, BQ-123, but not by an ETB antagonist, BQ-788. These results demonstrate that the contraction induced by ET-1 is totally mediated exclusively by ETA, but that Ca2+ entry through NSCCs in addition to L-VOCs plays an important role in contractions induced by low concentrations of ET-1, whereas it plays only a minor role in contractions induced by high concentrations of ET-1.

Animals↗
PubMed2005

Interventions for relieving pain associated with panretinal photocoagulation: a prospective randomized trial.

PURPOSE: To evaluate the efficacy of pain relief by oral diazepam, acetaminophen, mefenamic acid, intramuscular ketorolac tromethamine, and peribulbar anaesthesia in panretinal photocoagulation (PRP). METHODS: A total of 220 patients with proliferative diabetic retinopathy requiring PRP treatment were enrolled in this study. Before laser treatment, the patients were allocated randomly to one of eight groups: group 1: diazepam (n=22), group 2: acetaminophen (n=21), group 3: mefenamic acid (n=21), group 4: diazepam and acetaminophen (n=22), group 5: diazepam and mefenamic acid (n=22), group 6: peribulbar anaesthesia with lidocaine (n=23), group 7: intramuscular injection of ketorolac tromethamine (n=22), group 8: placebo (n=67). Pain after the laser treatment was assessed by a verbal descriptive scale. Blood pressure and heart rate were measured before and after laser treatment. RESULTS: Patients receiving peribulbar anaesthesia had a significantly lower pain score than the control group (P<0.0001). Additionally, the peribulbar anaesthesia-treated group had the significantly least PRP-associated rise in either systolic (P=0.043) or diastolic blood pressure rates (P=0.030). There were no significant differences in pain score using other anesthetic agents when compared with the control group. There were no significant changes in heart rate after PRP treatment. CONCLUSION: Peribulbar anaesthesia is effective in reducing pain and blood pressure increase after PRP treatment. Oral diazepam, mefenamic acid, and acetaminophen (either alone or in combination with each other) are not effective in preventing PRP treatment-associated pain. Intramuscular injection of ketorolac tromethamine is also not effective in reducing PRP-associated pain.

Acetaminophen↗
PubMed1999

The action of flufenamic acid and other nonsteroidal anti-inflammatories on sulfate transport in the isolated perfused rat liver.

The influence of flufenamic acid and other nonsteroidal anti-inflammatories on sulfate transport in the liver was investigated. The experimental system was the isolated perfused rat liver. Perfusion was accomplished in an open, nonrecirculating system. The perfusion fluid was Krebs/Henseleit-bicarbonate buffer (pH 7.4), saturated with a mixture of oxygen and carbon dioxide (95:5) by means of a membrane oxygenator and heated to 37 degrees C. Sulfate transport (equilibrium exchange) was measured by employing the multiple-indicator dilution technique with simultaneous injection (impulse input) of [35S]sulfate. [3H]sucrose (indicator for the distribution of the sinusoidal transit times), and [3H]water (indicator for the total aqueous space). Analysis was accomplished by means of a space-distributed variable transit time model. Flufenamic acid and other anti-inflammatories inhibited sulfate transport in the liver. For a concentration of 100 microM, the following decreasing series of potency could be established: flufenamic acid (53.4 +/- 2.9%) > niflumic acid (41.1 +/- 1.4%) > mefenamic acid (35.6 +/- 3.3%) > piroxicam (16.6 +/- 1.9%) > naproxen (13.5 +/- 8.4)%) nimesulide (11.6 +/- 5.8%). Inhibition of sulfate transport by flufenamic acid was clearly concentration dependent; 250 microM flufenamic acid produced more than 95% inhibition. Flufenamic acid in the range between 50 and 250 microM did not affect the mean transit times of tritiated water (t water) and [3H]sucrose (t suc), the same applying to all other anti-inflammatory agents (100 microM) tested in this work. This means that these agents do not affect vascular and cellular spaces, even when present at high concentrations. The ratio of the intra- to extracellular sulfate concentrations ([C]i/[C]e), generally between 0.4 and 0.5 under control conditions, was affected only by 250 microM flufenamic acid and 100 microM niflumic acid. In the first case, this phenomenon is possibly due to the high degree of transport inhibition (more than 95%), which does not allow a uniform tracer distribution over the whole cellular space during a single passage through the liver. The degree of inhibition of sulfate transport by 100 microM flufenamic acid was a function of the concentration of nontracer sulfate. With sulfate in the range between 1.2 and 25 mM, the inhibition degree increased linearly with the concentration. In the presence of flufenamic acid, the saturation curve of equilibrium exchange showed a substrate inhibition-like phenomenon, which was absent in the control curve. As inhibitors of sulfate transport in hepatocytes, flufenamic and niflumic acids are less active than in erythrocytes by a factor of 10(2). This observation is most probably indicative of structural differences between the hepatic sulfate carrier and the anion carrier of erythrocytes. It is unlikely that the action of flufenamic acid and its analogs on sulfate transport is a consequence of energy metabolism inhibition. Nimesulide is as active as flufenamic or niflumic acid in inhibiting energy metabolism but considerably less efficient as an inhibitor of sulfate transport. Our results as well as literature data reveal that the interactions of the nonsteroidal anti-inflammatories with the liver membranes and intracellular structures are ample and complex. Even at high concentrations, however, these interactions are not so intense as to change the vascular and cellular spaces.

Animals↗
PubMed1997

Comparison of the nitric oxide and cyclo-oxygenase pathway in mesenteric resistance vessels of normotensive and spontaneously hypertensive rats.

1. The double perfused mesentery was used to compare arterial and venous KCl- and acetylcholine (ACh)-induced responses in tissues taken from normotensive (WKY) and spontaneously hypertensive rats (SHR) in the presence or absence of inhibitors of nitric oxide (NO) synthase (NG-nitro-L-arginine (L-NOARG) and NG-nitro-L-arginine methyl ester (L-NAME)) and cyclo-oxygenase (indomethacin, mefenamic acid). 2. KCl (20 to 120 mM K+) caused concentration-dependent increases in arterial and venous perfusion pressures. The maximal arterial effects were significantly higher in the SHRs than in the WKY, with no differences in the venous pressor responses. 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. 4. L-NAME and L-NOARG (100 microM) potentiated the pressor responses to KCl to the same extent in the venous and arterial beds derived from WKY and SHR, while indomethacin and mefenamic acid (5 microM) only significantly decreased these responses in WKY. 5. Acetylcholine (ACh)-induced relaxations (1 nM to 10 microM) were significantly higher in arterial beds of WKY than in SHR, without differences in the venous relaxant responses. 6. L-NAME (100 microM) inhibited ACh-induced relaxations in arterial and venous beds from both groups of rats. Mefenamic acid was without effect on ACh-induced relaxations in either the arterial or the venous beds from WKY and SHR. 7. In conclusion, the liberation of NO in the perfused mesenteric vasculatures requires an active tone and no dysfunction of NO synthase activity is functionally apparent in the mesenteries isolated from SHRs. The cyclo-oxygenase pathway is only implicated in the KCl-induced responses of tissues derived from WKY, but not in the vasodilatations induced by ACh in either the arterial or the venous vasculatures from WKY and SHR.

Acetylcholine↗
PubMed1992

Activation of nonselective cation channels in the basolateral membrane of rat distal colon crypt cells by prostaglandin E2.

Ion channels in the basolateral membrane of colonic crypts were investigated with the patch-clamp technique during stimulation of secretion. Intact crypts were isolated from rat distal colon and the cell potential was recorded by addition of nystatin to the pipette solution. The cell resting potential in the base of the crypt was -74 +/- 1 mV (n = 90). Addition of 100 microM carbachol to the bath resulted in a transient hyperpolarization by 9 mV, which was probably due to the opening of basolateral K+ channels. In contrast, application of prostaglandin E2 (PGE2, 1 nM-1 microM) caused a dose-dependent depolarization in the base of the crypt. With 1 microM PGE2 cells depolarized from -74 +/- 1 to -27 +/- 2 mV (n = 26). Cell potential recordings in the midcrypt showed only a slight and transient depolarization after application of PGE2, whereas cells close to the surface of the crypt had no response. In the base of the crypt the PGE2-induced depolarization could be completely inhibited by addition of 50 microM flufenamic acid, a known blocker of nonselective cation channels. After substitution of all monovalent cations by N-methyl-D-glucamine in the bath, PGE2 had no significant effect on the cell potential. Cell-attached experiments with no nystatin in the patch pipette revealed the activation of ion channels in the basolateral membrane after application of PGE2. After excision of the membrane patch, these channels could be identified as nonselective cation channels. Experiments involving substitution of the bath solution showed that the channel is impermeable for Cl- and scarcely permeable for Ca2+ ions. The permeability sequence for monovalent cations, as calculated from reversal potentials, is NH4+ greater than Na+ = K+ greater than Rb+ = Li+ much greater than TRIS+ = NMDG+. Single channels are completely inhibited by flufenamic acid (50 microM), mefenamic acid (200 microM), as well as by 3',5-dichlorodiphenylamine-2-carboxylate. In conclusion, PGE2 activates nonselective cation channels in the basolateral membrane of cells in the base of colonic crypts. It is suggested that this mechanism initiates the secretion of K+ ions. Na+ influx through the nonselective cation channel will stimulate the Na+/K+ pump and active uptake of K+ at the basolateral side. K+ can leave the cell at the luminal side through K(+)-selective channels.

Animals↗
PubMed1988

Gas chromatographic analysis of flunixin in equine urine after extractive methylation.

A quantitative method for the analysis of flunixin, 2-(2-methyl-3-trifluoromethylanilino) nicotinic acid, in equine urine by gas chromatography with nitrogen-phosphorus detection has been developed. Flunixin and the internal standard, mefenamic acid, N-(2,3-xylyl) anthranilic acid, were analysed after extractive methylation of the carboxylic acid group using methyl iodide. The extraction and alkylation conditions of flunixin and mefenamic acid have been studied. The detection limit of the method was 0.25 mumol/l flunixin in urine (74 ng/ml). Flunixin was found to be conjugated to 96.5% in equine urine, and the conjugate was spontaneously hydrolysed to free flunixin. This approach can also be used to confirm the presence of flunixin or mefenamic acid in horse urine in the doping control of racehorses.

Alkylation↗
PubMed2001

Increased urinary uronic acid excretion in experimentally-induced renal papillary necrosis in rats.

We have evaluated the potential of urinary uronic acid measurement as an early indicator in the development of renal papillary necrosis (RPN). Urinary uronic acid was quantified with a range of other urinary biochemical parameters in rats given multiple doses of N-phenylanthranilic acid (NPAA) or mefenamic acid (MFA), each of which induces a dose-related papillary necrosis. In addition, histological examination was also carried out to confirm the development and presence of RPN. NPAA was administered to male wistar rats at p.o. doses of 100, 250, and 500 mg/kg and MFA at p.o. doses of 75, 150, and 300 mg/kg on days 1-4 and 8-11, and urine samples were collected for 16 hours each day. NPAA increased uronic acid excretion two-fold for both medium and high doses from day four. MFA increased uronic acid excretion to two and a half-fold by day 10 in the highest dose administered. Urinary creatinine was equally elevated in a dose-related manner following treatment with either NPAA or MFA. None of the other routine markers (urinary or serum) of nephrotoxicity showed any statistical changes. NPAA produced a dose- and time-related increase in excretion of uronic acid. Evidence of widespread papillary necrosis was seen histologically at the high doses of NPAA or MFA. The significant elevation of uronic acid in urine following treatment with either NPAA or MFA was well ahead of the development of RPN detectable by routine histology, suggesting that uronic acid measurement could serve as an early indicator of RPN. The assessment of urinary uronic acid may therefore provide a novel sensitive and selective marker of identifying the lesion earlier than is currently possible. An increase in urinary uronic acid following NPAA and MFA treatment supports the biochemical basis of these changes as a representative of acid mucopolysaccharides accumulation.

Animals↗
PubMed1988

Inhibition of postpyrogenic increase of phagocytic and killing activity of neutrophils by nonsteroid antiinflammatory drugs.

Acetylsalicylic acid (300 mg/kg), mefenamic acid (30 mg/kg) or indomethacin (20 mg/kg) given orally in the doses preventing the postpyrogenic fever, inhibited the stimulatory effect of LPS on phagocytic and killing activity of neutrophils. The dose of acetylsalicylic acid that did not eliminate fever in rabbits (100 mg/kg), had no suppressive effect upon fever-stimulated killing activity of neutrophils. The drugs administered twice a day to normothermic animals did not evoke any suppressive changes in the activity of neutrophils.

Animals↗
PubMed2006

Skin permeation enhancement potential of Aloe Vera and a proposed mechanism of action based upon size exclusion and pull effect.

The aim of this study was to determine in vitro the potential of Aloe Vera juice as a skin permeation enhancer; a secondary aim was to probe the extent to which Aloe Vera itself permeates the skin. Saturated solutions of caffeine, colchicine, mefenamic acid, oxybutynin, and quinine were prepared at 32 degrees C in Aloe Vera juice and water (control) and used to dose porcine ear skin mounted in Franz diffusion cells with water as receptor phase. Receptor phase samples were taken over a 48 h period and permeants determined by reverse-phase HPLC. For caffeine and mefenamic acid no significant enhancements occurred between Aloe Vera and water as vehicles (p>0.05). However, for colchicine, oxybutynin and quinine the presence of Aloe Vera within the formulation provided enhancements (p < or = 0.05). Enhancement potential was dependent upon the molecular weight of the drug in formulation, with the enhancement effect attributable to as yet unidentified components within the Aloe Vera. Colchicine, with a molecular weight of 399.44, achieved the best enhancement with an enhancement ratio of 10.97. No correlation with lipophilicity was apparent. In a further experiment, where freeze-dried Aloe Vera was reconstituted at 200% residue level, permeation of quinine was 2.8 x that from normal Aloe Vera, providing further evidence for the presence of an enhancing factor within Aloe Vera. Certain, although unidentified, components of Aloe Vera readily permeated skin and the relative amount by which they permeated skin was inversely related to the molecular weight of the drug in solution, thus enhancement ratio. A new mechanistic rationale is proposed whereby larger drug solutes inhibit the permeation of Aloe Vera components, but also are then able to interact more effectively with the enhancing factor and be subject to the pull effect.

Aloe↗
PubMed1985

Prostaglandins in the fetal circulation following maternal ingestion of a prostaglandin synthetase inhibitor during mid-pregnancy.

To assess the possible effect upon the fetus of maternal ingestion of the prostaglandin synthetase inhibitor, mefenamic acid, taken during mid-pregnancy (15-22 weeks) to prevent spontaneous abortion, samples of fetal blood were collected at fetoscopy from 13 treated and 14 untreated control cases. Mefenamic acid levels in the fetus were 32-54% of those in the mothers in the treated group, while prostaglandins E2 (PGE2), 6-oxo-PGF1 alpha and PGFM were all slightly but not significantly lower in those patients given 500 mg mefenamic acid 40-180 min prior to sampling than in untreated controls. Results indicate that the prostaglandin synthetase inhibitor crosses the placenta at this early gestation and may possibly suppress fetal prostaglandin production.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Renal humoral modulation of skeletal muscle tone in mice: implications for 'the pulmonary-renal cascade'.

The pulmonary-renal cascade may regulate the respiration and skeletal muscle contractility. To evaluate this working hypothetical model, we conducted experiments to ascertain the skeletal muscle tone of the Swiss mice (20-35 g). The animals were evaluated for their skeletal muscle tone via several techniques i.e. inclined plane test, grip strength test and swim test. Groups of mice (n=6) were pre-treated with mefenamic acid (60 mg/kg, i.p), carbenoxolone (100 mg/kg i.p) or vehicle only 15 minutes before the treatment with heparin (500 U/kg, i.v), urokinase (5500 U/kg, i.v) and erythropoietin (150 U/kg, i.v). Heparin potentiated the loss of skeletal muscle tone induced by mefenamic acid and carbenoxolone while urokinase & erythropoietin significantly enhanced the skeletal muscle tone as evaluated by all or one of the tests. Other groups of mice (n=6) were pretreated with mefenamic acid (1 mg i.c.v), carbenoxolone (160 microg i.c.v) or minoxidil (30 microg i.c.v) and the effects of heparin & urokinase and erythropoietin on skeletal muscle tone were evaluated. To study the effects of heparin and urokinase on nerve regeneration, two groups of mice underwent a sham and sciatic nerve crush procedure. The mice treated with urokinase recovered much faster as compared to those treated with heparin or saline. These experimental results suggest that gap junction blockers and potassium channel openers interact with heparin, urokinase and erythropoietin to control the skeletal muscle tone.

Animals↗
PubMed1996

Effect of heartworm infection on fade of norepinephrine-induced constriction in canine pulmonary vein.

OBJECTIVE: To test the possible role of endothelial cells in mediating fade of norepinephrine-induced constriction and the effect of heartworm infection on these responses. DESIGN: Rings of pulmonary vein from control and heartworm-infected dogs were constricted with norepinephrine (10(-5.5)M) and followed over 65 minutes. Time profiles were established by measuring active tension every 2 minutes for the first 10 minutes, then every 5 minutes for 15 minutes, then every 10 minutes for 40 minutes. Time profiles were done in pulmonary vein rings with and without endothelial cells, and in the presence and absence of N-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase inhibitor), mefenamic acid (cyclooxygenase inhibitor), or methylene blue (guanylate cyclase inhibitor). ANIMALS: 12 noninfected control and 11 heartworm-infected dogs. RESULTS: Pulmonary vein constricted with norepinephrine spontaneously loses tension (fades) over time. Fade was not different between control and heartworm-infected dogs. In pulmonary vein from control dogs, methylene blue decreased fade while L-NAME and mefenamic acid did not. In pulmonary vein from heartworm-infected dogs, L-NAME and methylene blue significantly decreased fade, but mefenamic acid did not. CONCLUSION: Nitric oxide, but not cyclooxygenase products, mediates fade of norepinephrine-induced constriction in pulmonary vein from heartworm-infected dogs. In control dogs, neither nitric oxide nor cyclooxygenase products appear to be involved in fade. We conclude that in canine pulmonary vein, fade of norepinephrine-induced constriction is mediated, in part, by endothelial cells. CLINICAL RELEVANCE: Altered production of endothelium-derived relaxing factors may be important in the pathogenesis of heartworm disease.

Animals↗
PubMed1991

1,2-Dihydro-3,1-benzoxazin-4-one and 4H-1,2-dihydro-pyrido-[2,3-d]- [1,3]-oxazin-4-one derivatives as potential prodrugs. Part III: Permeability through excised human skin in vitro.

The percutaneous permeation characteristics of 6 potential prodrugs 2-7 in comparison with their parent drug mefenamic acid (1) in vitro using excised human skin were studied. The results show that all potential prodrugs tested were at least 2.0 times as effective as mefenamic acid; compounds 2 and 7 permeated almost 5 times as quickly as mefenamic acid through excised human skin. The relations between the permeation behaviour, the RM values and the melting points were interpreted.

Humans↗