Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D00527 (Nedocromil sodium)
 190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A single dose double-blind crossover study was performed to compare the efficacy of nedocromil sodium (4 mg) and placebo administered from pressurized aerosols against bronchoconstriction induced by the inhalation of ultrasonically nebulized distilled water (fog) in twelve asthmatic subjects. Neither active nor placebo pre-treatment produced any significant change in baseline FEV1 and SRaw. Nedocromil sodium significantly attenuated fog-induced falls in FEV1 (P less than 0.001) and increased specific airways resistance (SRaw, P less than 0.01). The results provide further evidence of the potential therapeutic usefulness of nedocromil sodium in the management of chronic obstructive airways disease.
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PMID:Prevention of fog-induced bronchospasm by nedocromil sodium. 303 May 81

Nedocromil sodium, a disodium salt of a pyroquinolinedicarboxylic acid, raises the bronchial hyperresponsiveness threshold, because it inhibits the mediators released by the various cells, and reduces the involvement and activation of inflammatory cells. The aim of this study was to evaluate the state of activation of the immunocompetent cells and the main chemical mediators present in the bronchoalveolar lavage (BAL) fluid from 10 atopic asthmatic patients, before and after treatment with nedocromil sodium. The following examinations were performed before treatment and after 120 days of therapy with nedocromil sodium at 16 mg/day (two 2-mg puffs x 4): the level of chemical mediators and the state of activation of immunocompetent cells in BAL fluid; immunological analytes in activation of immunocompetent cells in BAL fluid; immunological analytes in peripheral blood; aspecific bronchial challenge test with ultrasonicated bidistilled H2O fog to evaluate variations in the hyperreactivity threshold; questionnaire to determine any adverse effects of treatment (cough, breathlessness, sleep disorders). Our findings demonstrate that nedocromil sodium prevents the release of chemotactic and inflammatory mediators by the effector cells and thus stabilizes microvascular permeability and epithelial damage, so raising the threshold of response to bronchoconstriction stimuli. Lastly, nedocromil sodium is associated with a better preventive therapeutic efficacy and good tolerance and can therefore be suggested as a valid drug to be used in the long-term treatment of bronchial asthma.
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PMID:Protective effects of nedocromil sodium on cellular and biohumoral components present in the bronchial alveolar lavage fluid and in peripheral blood in atopic asthmatics. 797 6

There is increasing evidence that the sensory nerves of the airway play a role in the asthmatic response. Nerve endings are exposed by the epithelial shedding that occurs with asthma. They may become sensitized and activated by inflammatory mediators and may release neuropeptides that then spread and amplify the inflammatory process in the airways. Nedocromil sodium may prevent the sensory nerves from becoming sensitized and inhibit their activation. This possibility is suggested because nedocromil is highly effective against several indirect challenges that involve sensory nerve stimulation. Nedocromil sodium was able to inhibit the bronchoconstriction induced in patients with asthma by exposure to bradykinin, sulfur dioxide, metabisulfite, and ultrasonically nebulized water. Cough, which is a prominent symptom of asthma, is believed to be a result of sensory nerve activation. In several long-term clinical studies, nedocromil sodium reduces the severity of cough among patients with asthma. Studies are needed to define how nedocromil sodium acts on the sensory nerves.
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PMID:Effect of nedocromil sodium on airway sensory nerves. 839 25

Nedocromil sodium is used in the treatment of reversible obstructive airways diseases, such as asthma. The physicochemical, mechanical, and biological characteristics of nedocromil sodium can be altered by its conversion to other salt forms. In this study, three crystalline hydrates, the pentahydrate, heptahydrate, and decahydrate, of a bivalent metal salt, nedocromil magnesium (NM), were prepared. The relationships between these hydrates were studied through their characterization by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA). Karl Fischer titrimetry (KFT), hot stage microscopy (HSM), ambient or variable temperature powder X-ray diffraction (PXRD), Fourier-transform infrared (FTIR) spectroscopy, solid-state nuclear magnetic resonance (SSNMR) spectroscopy, scanning electron microscopy (SEM), water uptake at various relative humidities (RH), intrinsic dissolution rate (IDR), and solubility measurements. The pentahydrate showed two dehydration steps, corresponding to two binding states of water, a more temperature-sensitive tetramer and a more stable monomer, deduced from the crystal structure previously determined. The heptahydrate and decahydrate each showed a dehydration step with a minor change in slope at about 50 degrees C, which was analyzed by derivative TGA and confirmed by DSC. HSM and variable temperature PXRD also confirmed the thermal dehydration behavior of the NM hydrates. The decahydrate underwent an apparently irreversible phase transformation to the pentahydrate at 75 degrees C at an elevated water vapor pressure. The PXRD, FTIR, and SSNMR of the decahydrate were similar to those of the heptahydrate, suggesting that the three extra water molecules in the decahydrate are loosely bound, but were significantly different from those of the pentahydrate. The rank order of both IDR and solubility in water at 25 degrees C was heptahydrate approximately decahydrate > pentahydrate, corresponding to the rank order of free energy with respect to the aqueous solution.
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PMID:Physicochemical characterization of nedocromil bivalent metal salt hydrates. 1. Nedocromil magnesium. 889 66

Nedocromil sodium, which is used in the treatment of reversible obstructive airway diseases, such as asthma, is found to exist in the following hydrate phases: the heptahemihydrate, the trihydrate, a monohydrate, and an amorphous phase which contains variable amounts of water (1.5-3.0 mol). An anhydrate phase is formed from the trihydrate at zero humidity at >/= 150 degrees C, but is rapidly hydrated under ambient conditions. The physical and thermodynamic properties of the four hydrate phases were characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD) at ambient and elevated temperatures, hot-stage microscopy (HSM), solid phase interconversion at various relative humidities (RH), intrinsic dissolution rate (IDR), equilibrium solubility measurements, and critical RH measurements. Below 100 degrees C in open pan TGA, the heptahemihydrate and the amorphous forms lose virtually all their water, the monohydrate loses negligible amounts of water, whereas the trihydrate loses the first two moles of water. From 130 degrees C to 200 degrees C in open pan TGA the trihydrate and the monohydrate lose their last mole of water to form the anhydrate. In crimped pan DSC, the thermal events observed are analogous to those observed in open pan TGA, but the temperatures are increased by about 75 degreesC for all except the heptahemihydrate, for which the thermal events are more complex. When the heptahemihydrate is heated in a crimped pan, a melting endotherm is observed at about 75 degrees C followed by three dehydration endotherms. For the crystalline hydrate phases at 22 degrees C, the ranges of stability are as follows: the monohydrate from 0 to 6.4% RH; the trihydrate from 6.4 to 79.5% RH; the heptahemihydrate above 80% RH. A microbalance study showed that the heptahemihydrate is kinetically stable over the range 11 to 79.5% RH. The IDR in water at 25 degrees C under constant hydrodynamic conditions decreases in the rank order: monohydrate > trihydrate > heptahemihydrate, corresponding to the rank order of free energy with respect to the aqueous solution. The equilibrium aqueous solubility of the heptahemihydrate at 25.0 +/- 0.2 degrees C is 0.956 +/- 0.010 M.
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PMID:Physical characterization of nedocromil sodium hydrates. 972 54

Three different powder preparations of the drug disodium 9-ethyl-4, 6-dioxo-10-propyl-4H,6H pyrano[3,2-g]quinoline-2,8-dicarboxylic trihydrate, Nedocromil sodium (trade name Tilade), have been fully dehydrated in a vacuum and their water vapor adsorption characteristics quantitatively assessed at different water vapor pressures over a temperature range 20 to 40 degrees C. At saturated vapor pressures, 100% RH, rates of adsorption are around 0.1 s(-1/2). Graphs of square root of time against reduced mass during uptake of water vapor at vapor pressures in the range 20 to 47 mm of Hg, all equivalent to 100% RH, indicate control by a diffusion mechanism with activation energies in the range 8 to 24 kJ mol(-1), dependent on the powder preparation method. In two of the powders nonlinear Arrhenius-type plots are interpreted as showing that control of the process is dependent on the surface's ability to hold water molecules at the experimental temperature. The variation in activation energies and the calculated values for diffusivities, around 1 x 10(-13) m(2) s(-1), are used to explore structural involvement in the overall water adsorption process. The measured values of water vapor diffusivity into the structure have been used to predict the water solubility of nedocromil sodium trihydrate, and the results show good agreement to reported solubilities. This approach to solubility prediction is an alternative to the Noyes and Whitney method where ions leaving the surface are monitored.
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PMID:Adsorption of water by anhydrous nedocromil sodium from 20 to 40 degrees C. 1043 May 42

Exercise-induced bronchospasm, exercise-induced bronchoconstriction, and exercise-induced asthma (EIA) are all terms used to describe the phenomenon of transient airflow obstruction associated with physical exertion. It is a prominent finding in children and young adults because of their greater participation in vigorous activities. The symptoms shortness of breath, cough, chest tightness, and wheezing normally follow the brief period of bronchodilation present early in the course of exercise. Bronchospasm typically arises within 10 to 15 minutes of beginning exercise, peaks 8 to 15 minutes after the exertion is concluded, and resolves about 60 minutes later, but it also may appear during sustained exertion. EIA occurs in up to 90% of asthmatics and 40% of patients with allergic rhinitis; among athletes and in the general population its prevalence is between 6% and 13%. EIA frequently goes undiagnosed. Approximately 9% of individuals with EIA have no history of asthma or allergy. Fifty percent of children with asthma who gave a negative history for EIA had a positive response to exercise challenge.6 Among high school athletes, 12% of subjects not considered to be at risk by history or baseline spirometry tested positive. Before the 1984 Olympic games, of 597 members of the US team, 67 (11%) were found to have EIA. Remarkably, only 26 had been previously identified, emphasizing the importance of screening for EIA even in well-conditioned individuals who appear to be in excellent health. The severity of bronchospasm in EIA is related to the level of ventilation, to heat and water loss from the respiratory tree, and also to the rate of airway rewarming and rehydration after the challenge. Postexercise decrease in the peak expiratory flow rate of normal children may be as much as 15%; therefore, only a decrease in excess of 15% should be viewed as diagnostic. EIA is usually provoked by a workload sufficient to produce 80% of maximum oxygen consumption; however, in severe asthmatics even minimal exertion may be enough to produce symptoms. Patients with normal lung function at rest may have severe air flow limitation induced by exercise,10 and as many as 50% of patients who are well-controlled with inhaled corticosteroids still exhibit EIA. A challenge of sufficient magnitude will provoke EIA in all patients with asthma. PHARMACOLOGIC THERAPY: Exercise, unlike exposure to allergens, does not produce a long-term increase in airway reactivity. Accordingly, patients whose symptoms manifest only after strenuous activity may be treated prophylactically and do not require continuous therapy. Most asthma medications, even some unconventional ones such as heparin, furosemide, calcium channel blockers, and terfenadine, given before exercise, suppress EIA. McFadden accounts for the efficacy of these disparate classes of drugs by their potential effect on the bronchial vasculature that modulates the cooling and/or rewarming phases of the reaction. Short-acting -agonists provide protection in 80% to 95% of affected individuals with insignificant side effects and have been regarded for many years as first-line therapy. Two long-acting bronchodilators, salmeterol and formoterol, have been found effective in the prevention of EIA.18-21 A single 50-microg dose of salmeterol protects against EIA for 9 hours; its duration appears to wane in the course of daily therapy. Cromolyn sodium is highly effective in 70% to 87% of those diagnosed with EIA and has minimal side effects. Nedocromil sodium provides protection equal to that of cromolyn in children. Children commonly engage in unplanned physical activity and sometimes are not allowed to carry their own medication. Thus, a simple long-acting regimen given at home is likely to be more effective than short-acting drugs that must be administered in a timely manner. Although the 12-hour protection by salmeterol reported by Bronsky et al may not persist with continued use, the 9-hour duration of action is
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PMID:Keeping children with exercise-induced asthma active. 1046 21

This study was designed to test the hypothesis that nedocromil sodium inhibits sensory nerve function to reduce flare and itch in human skin. Nedocromil sodium (2%) or water (control) was introduced into the volar forearm skin of eight non-atopic volunteers by iontophoresis (8 mC) and histamine (20 microl of 1 microM and 300 nM) injected intradermally 10 min later at the same site. Itch was assessed on a visual analogue scale every 20 s for 5 min. Weal and flare areas and mean blood flux within the flare were assessed by scanning laser Doppler imaging at 10 min. The results showed that nedocromil sodium reduced itch scores, totalled over 5 min, by approximately 74.0% (P<0.005) and flare areas by approximately 65% (P<0.03). Neither weal areas nor blood flux within were reduced. These data demonstrate that nedocromil sodium is effective in reducing neurogenic itch and flare in the skin. We suggest that its mechanism of action is modulation of sensory neurone activation or conduction in the skin.
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PMID:Nedocromil sodium inhibits histamine-induced itch and flare in human skin. 1115 12

Inhalation of ultrasonically nebulised distilled water (fog) induces cough; however, the receptor type(s) mediating this reflex are poorly defined. In humans, cough threshold can be determined by inhalation of progressively increasing fog concentrations; the intensity of the associated motor response can be indexed in terms of flow-related variables as well as of the peak and slope of the integrated electromyographic activity of the abdominal muscles. We have evaluated coughing in patients with Parkinson's disease who show a high incidence of serious chest infections. These patients turned out to have a normal cough threshold but reduced expiratory muscle force during reflex coughing; this suggests an impairment in the central mechanisms subserving muscle activation possibly leading to inefficient airway clearing. Recurrent chest infections also affect laryngectomised patients. These patients have a normal cough threshold but reduced muscle force during coughing in response to threshold stimuli. Voluntary coughing is preserved in these patients, and this should be used to facilitate mucus removal. In normal subjects, fog inhalation causes cough and increases in respiratory drive and minute ventilation, mainly accounted for by increases in tidal volume, possibly due to activation of airway rapidly adapting receptors. Nedocromil sodium administration increases cough threshold and attenuates the ventilatory responses. The assessment of sensory and motor components of coughing may represent a useful tool for those investigating cough in humans.
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PMID:Water aerosols and cough. 1209 73