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At least 793 records · Page 44Linked to original sources
PubMed1989

Meclofenamate increases ventilation in lambs.

To investigate the effects of the prostaglandin synthetase inhibitor, meclofenamate, on postnatal ventilation, we studied 11 unanaesthetised, spontaneously-breathing lambs at an average age of 7.9 +/- 1.1 days (SEM; range 5-14 days) and an average weight of 4.9 +/- 0.5 kg (range 3.0-7.0 kg). After a 30-min control period we infused 4.23 mg/kg meclofenamate over 10 min and then gave 0.23 mg/h per kg for the remainder of the 4 h. Ventilation increased progressively from a control value of 515 +/- 72 ml/min per kg to a maximum of 753 +/- 100 ml/min per kg after 3h of infusion (P less than 0.05) due to an increased breathing rate; the effects were similar during both high- and low-voltage electrocortical activity. There were no significant changes in tidal volume, heart rate, blood pressure, arterial pH or PaCO2, the increased ventilation resulted from either an increase in dead space ventilation or an increase in CO2 production. This study indicates that meclofenamate causes an increase in ventilation in lambs but no changes in pH of PaCO2. The mechanism and site of action remain to be defined.

Analysis of Variance↗
PubMed1989

Release of prostaglandin E2 from cells by photodynamic treatment in vitro.

Photodynamic treatment in vitro, using the photosensitizer Photofrin II and light at 630 nm, was found to liberate large amounts of prostaglandin E2 (PGE2) from mouse radiation-induced fibrosarcoma tumor cells and peritoneal macrophages, but not from L929 fibroblasts. PGE2 release was dose dependent and directly related to cell membrane disruption. It occurred rapidly and was complete within 30 min of treatment. PGE2 release could be inhibited by indomethacin, meclofenamate and extended prior exposure to dexamethasone, indicating that it was due to new production involving both the phospholipase and cyclooxygenase enzyme systems. Removal of calcium ions, necessary for phospholipase activation, from the medium did not inhibit the photodynamically induced elevated PGE2 production, possibly because of Ca2+ resupply from leaking intracellular pools.

Animals↗
PubMed1989

Meclofenamate does not affect lung development in fetal sheep.

Prostaglandins may be involved in some aspects of fetal lung development, including surfactant metabolism, tracheal fluid production, and possibly lung growth. In the fetus, during the days before delivery, plasma PGE2 concentration increases and concurrently, tracheal fluid production decreases and surfactant production increases. To determine whether the increase in PGE2, specifically plasma PGE2 concentration, is responsible for these changes, we continuously infused the prostaglandin synthetase inhibitor, meclofenamate (0.7 mg/h per kg), into 8 fetal sheep for 5-13 days before delivery; 5 control fetuses received a continuous infusion of solvent for 5-11 days before delivery. Meclofenamate infusion significantly decreased plasma PGE2 concentrations until the day of delivery. However, meclofenamate did not affect tracheal fluid production or its decrease before delivery, fetal plasma cortisol concentration, surfactant content of tracheal fluid and lung tissue, organ weights, lung weights, or lung DNA and protein content. We conclude that the changes in lung development during the days before delivery are not dependent on the usual high fetal plasma concentration of PGE2 or its increase before delivery.

Animals↗
PubMed1979

Effect of drugs on the force of spontaneous mechanical activity in rat portal vein.

A study was made on the force of spontaneous mechanical activity in the rat portal vein. Prostaglandin inhibitor, sodium meclofenamate, phosphodiesterase inhibitors, aminophylline and dipyridamole, adenosine and blockade of calcium entry by isoptin all reduced the force of spontaneous activity in a concentration-dependent manner, while imidazole enhanced it. Low concentration of aminophylline (10 microM), dipyridamole (6 microM) and meclofenamate (10 microM) depressed the spontaneous contraction of the vein by about 50% without modifying the response to noradrenaline. At higher concentration of these drugs, spontaneous mechanical contraction was reduced further and the response to noradrenaline antagonized. Low concentration of isoptin also reduced the mechanical activity without affecting maximum response to noradrenaline. A common mechanism of action for the drugs tested, namely the limiting of Ca2+ availability for muscular contraction, is discussed. Adenosine markedly reduced the spontaneous mechanical activity of the rat portal vein. Its relaxation effect could be due to the activation of a specific adenosine receptor.

Adenosine↗
PubMed1989

Meclofenomate inhibition of UV-induced erythema--a randomized, placebo-controlled, double-blind study.

Systemic intradermal and topical inhibitors of eicosanoid synthesis have been shown to decrease the intensity delay the onset of erythema produced with a single exposure to ultraviolet (UV) light. We studied the effect of single and multiple doses of meclofenomate on erythema induced by single and multiple doses of UV light. Thirty Caucasian subjects took either meclofenomate 100 mg t.i.d. or matching placebo for 5 days, crossing over to the alternative for 5 more days after a 2-day washout period. A statistical analysis was made of erythema response immediately prior to the study and then on 8 successive days during the study. Analysis of single and multiple exposure data revealed a statistically significant inhibition of erythema from meclofenomate therapy as compared with placebo.

Adult↗
PubMed1989

Radio-protective effect of sodium meclofenamate. A prospective clinical trial.

Twentyfour patients treated with irradiation to either their pelvis or their chest for neoplastic disease were included in a randomized study of radioprotection with sodium meclofenamate (Meclomen) (SM). Seventeen patients received SM 100 mg, p.os, t.i.d., and seven received placebo. The long-range radiation related chronic gastrointestinal and urinary tract toxicity was diminished by SM. At 12 months post irradiation, SM treated patients experienced less gastrointestinal and urinary symptoms, as well as less measured bladder contraction, than the controls. Acute gastrointestinal signs of radiotoxicity, however, seemed to have been enhanced by SM. The treated patients suffered from nausea, vomiting, and diarrhea. These acute toxic effects were temporary and reversible.

Adult↗
PubMed1985

Vascular effects of Physalia physalis venom in the skeletal muscle of the dog.

The purpose of this study was to characterize the mode of action of the venom from Portuguese man-of-war (Physalia physalis) on the skeletal muscle vascular bed of dogs anesthetized with sodium pentobarbital (35 mg/kg). Venous outflow and the blood pressure difference across the hind-limb vascular bed were used to calculate changes in resistance due to close arterial injections of the venom (0.001-1 microgram/kg). The venom consistently produced dilations that were blocked by sodium meclofenamate (5 mg/kg). Atropine (1 mg/kg), propranolol, phentolamine, cimetidine (each 2 mg/kg) or tripelennamine (2.5 mg/kg) had no significant blocking effect. The venom also produced transient dilations on vascular beds predilated with histamine or prostaglandin E1, or preconstricted with norepinephrine (each 0.01 microgram/kg) or by sympathetic stimulation (12 V, 20 Hz). These data suggest that Physalia venom dilates skeletal muscle vasculature primarily by stimulation of endogenous prostaglandin synthesis.

Alprostadil↗
PubMed1986

Effect of Portuguese man-of-war venom on isolated vascular segments.

The purpose of this study was to characterize the mode of action of nematocyst venom from the Portuguese man-of-war (Physalia physalis) on isolated rabbit arterial ring segments, and to see if these in vitro effects were similar to those observed in the intact skeletal muscle vasculature of the dog (see Loredo et al., J. Pharmacol. Exp. Ther. 232: 301-304, 1985). The venom (0.021-4.28 micrograms/ml) produced dose-dependent relaxations of norepinephrine precontracted arterial segments from various vascular beds. Venom-induced relaxations were blocked by sodium meclofenamate (10-20 micrograms/ml), but not by atropine (6 micrograms/ml), propranolol (4-12 micrograms/ml) or quinacrine (2-4 X 10(-5) M). These results were similar to those observed in the intact skeletal muscle vascular bed of the dog and further implicate the stimulation of endogenous prostaglandin synthesis as the mechanism by which P. physalis venom dilates vasculature.

Animals↗
PubMed1978

Acute systemic anaphylaxis in adult domestic fowl--possible role of vasoactive lipids and peptides.

Bovine albumin (BA: 2 mg/kg-1, i.v.) produced a fall in systemic arterial blood pressure accompanied by central venous hypertension and bradycardia in pentobarbital-anaesthetized, spontaneously breathing, bovine albumin-sensitized adult domestic fowl. Trasylol (a potent inhibitor of kallikreins) suppressed acute systemic anaphylaxis. Polyphloretin phosphate (an effective antagonist of PGF2alpha) also inhibited the cardiovascular responses to antigen and PGF2alpha. Sodium meclofenamate and phenylbutazone showed varying degree of blockade of cardiovascular responses to exogenously administered chemical mediators (bradykinik, PGF2alpha, SRS-A and to a lesser extent of histamine, 5-HT and acetylcholine) and antigen. Indomethacin (virtually devoid of receptor blocking activities toward exogenously injected chemical mediators) inhibited anaphylaxis. The results of this investigation strongly suggested an important role of vasoactive lipids and polypeptides in avian anaphylaxis.

Anaphylaxis↗
PubMed1988

Effects of salicylate vs. aspirin on renal prostaglandins and function in normal and sodium-depleted dogs.

The effects of aspirin (acetylsalicylate) (ASA) and nonsteroidal antiinflammatory drugs (NSAIDs) on renal prostaglandin (PG) biosynthesis and function have been studied extensively. In contrast, the in vivo effects of a nonacetylated salicylate (SA), such as sodium SA, on renal function have not been well characterized. No studies have examined the effects of SA on renal function in a situation in which the maintenance of normal kidney function is dependent upon intact renal PG synthesis (i.e., sodium restriction-elevated plasma renin activity). To evaluate the effects of SA vs ASA and/or a NSAID, normal and sodium-restricted anesthetized dogs were treated with SA and then meclofenamate (MECLO) or ASA followed by MECLO. In the normal animals, SA significantly decreased renal PGE2 and PGF2 alpha excretion. After SA a significant amount of MECLO-suppressible PGE2 and PGF2 alpha synthesis remained intact. Compared to SA, with ASA there was a greater decrease in PG excretion, with no further decrease in PG excretion with subsequent MECLO treatment. In the sodium-restricted animals (plasma renin activity, 18-24 ng of angiotensin l/ml/hr) ASA decreased PGE2 excretion but SA did not. In these animals SA did not cause renal vasoconstriction. Additional groups of sodium-restricted animals were studied with extremely high doses of ASA and SA (90 mg/kg) to elevate plasma SA to 200 to 250 micrograms/ml. In these animals SA did decrease PGE2 excretion significantly, but only to levels seen typically in normal animals and, after SA, a large amount of PGE2 excretion could be suppressed by MECLO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1977

Effects of antipyretic agents on fever and ruminal stasis induced by endotoxins in conscious goats.

Intravenous injection of endotoxin (LPS) from S. typhimurium (3,3 microng per kg body weight) or E. coli O111B4 (0,1 microng per kg body weight) caused fever and stasis of the forestomach contractions in conscious goats. Pretreatment with non-steroidal anti-inflammatory agents only had a partial antagonistic influence upon endotoxin induced ruminal stasis. In this respect, acetaminophen was the most potent drug of all agents tested. In dependence of the doses used, the following rank order of potency can be given in relation to the antipyretic activity: sodium flurbiprofen, sodium meclofenamate, acetaminophen, sodium novaminsulphonum and phenylbutazone. In the goat, sodium flurbiprofen (2 mg per kg i.v.) is a very potent and long acting antipyretic agent. It seems unlikely that the inhibition of forestomach motility by endotoxins is simple due to a release of prostaglandins. Since the inhibition also occurred in absence of a febrile response, it is concluded that the inhibition is not primarily due to hyperthermia.

Acetaminophen↗
PubMed1987

The dynamics of nonsteroidal anti-inflammatory therapy for primary dysmenorrhea.

The dynamics of drug therapy are generally discussed in terms of absorption, excretion, and blood levels. These established methods of analyzing the pharmacodynamics frequently fail to determine the more critical tissue concentrations necessary for ultimate drug action. The use of intrauterine pressures to objectively measure uterine response to drug therapy may be used to demonstrate the onset and magnitude of drug action in nonsteroidal anti-inflammatory drug therapy for patients with primary dysmenorrhea. When continuous intrauterine pressure data is combined with plasma drug level sampling, a reflection of the dynamics of these drugs may be possible. Data were studied from 18 patients who participated in a double-blind, placebo-controlled, single-dose crossover study of subjective and objective responses to meclofenamate. The responses in these patients indicated a clear parallel in time response curves between plasma drug level and alterations in uterine contractile activity. The slight time delay between the changes in blood drug level and the onset of changes in uterine activity is hypothesized to represent the time necessary to establish effective tissue levels. Examples of time response curves are illustrated.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1977

Nonsteroidal anti-inflammatory drugs: a review. New applications in hypersensitivity reactions of cattle and horses.

Nonsteroidal anti-inflammatory drugs inhibit the biosynthesis of kinins and prostaglandins and stabilize leukocyte lysosomal membranes. Nonsteroidal anti-inflammatory drugs also weakly block the biosynthesis of histamine and serotonin, and pharmacologically antagonize kinins, prostaglandins and slow-reacting substance of anaphylaxis. Nonsteroidal anti-inflammatory drugs effectively control both cardiovascular and respiratory manifestations of hypersensitivity in cattle and horses. This, coupled with the contrasting lack of effectiveness of "antiamine" drugs, suggests that bio-amines such as histamine and serotonin (5-hydroxytryptamine) may be less important than kinins, postaglandins and slow-reacting substance in the mediation of the hypersensitivity/inflammatory reaction, at least in cardiopulmonary systems of these species. Nonsteroidal anti-inflammatory drugs justify more prominence in the clinical control of acute respiratory disease in domestic herbivores.

Anaphylaxis↗
PubMed1987

Double-blind comparison of meclofenamate sodium with codeine and placebo for the pain of episiotomy.

Meclofenamate sodium, a nonsteroidal anti-inflammatory agent, was compared at two dose levels (100 mg and 200 mg) with codeine (60 mg) and placebo in a double-blind, randomized study of 218 women after normal vaginal delivery. The purpose was to determine the analgesic efficacy and safety of meclofenamate sodium for the short-term treatment of acute episiotomy pain. Meclofenamate sodium was significantly better than placebo in most measures of pain relief and reduction of pain intensity. The 100-mg dose of meclofenamate sodium was significantly better than codeine in relieving pain. Adverse experiences with the study medications were minimal (6.4%). Patients receiving codeine reported more side effects than did those receiving either dose of meclofenamate sodium. Meclofenamate sodium is a safe, effective analgesic for acute episiotomy pain.

Adolescent↗
PubMed1987

Comparison of meclofenamate sodium with codeine and placebo for the treatment of episiotomy pain.

Meclofenamate sodium, a nonsteroidal anti-inflammatory drug with proven analgesic effects, was compared at two dose levels (200 mg and 100 mg) with codeine (60 mg) and placebo in a double-blind, randomized study of 327 women experiencing episiotomy pain after normal delivery. Meclofenamate sodium at either dose was significantly better than codeine or placebo in reducing pain intensity and increasing pain relief, and it had a longer duration of action. Adverse effects were minimal, and their frequency did not differ significantly among treatment groups. Meclofenamate sodium appears to be as safe as and more effective than codeine for the management of episiotomy pain.

Adolescent↗