piperidines and sulfuric-acid

A simple and highly sensitive spectrofluorimetric method was developed and validated for determination of the antidiabetic agent repaglinide (RG) in tablets. The proposed method is based on measurement of the native fluorescence of RG in 0.1 M H(2)SO(4)/methanol medium at 360 nm after excitation at 243 nm. The method showed a linear dependence of the relative fluorescence intensity on drug concentration over the range of 0.02-0.50 μg mL(-1) with lower detection limit of 6.0 ng mL(-1) and lower quantification limit of 18 ng mL(-1). The method was successfully applied for determination of RG in different tablets and the obtained results were in good agreement with those obtained by the official method. The proposed method was extended to investigate the kinetics of oxidative degradation of the drug. A proposal for the degradation pathway was postulated.

Topics: Carbamates; Drug Stability; Linear Models; Methanol; Piperidines; Solvents; Spectrometry, Fluorescence; Sulfuric Acids; Tablets; Temperature; Time Factors

We recently reported that airway hyperresponsiveness (AHR) induced by a 6-h exposure to sulfuric acid (H(2)SO(4)) was inhibited by either the neurokinin (NK)-1 receptor antagonist, FK888, or the NK-2 receptor antagonist, SR48968, when administered immediately before the exposure. The aims of this study were to determine whether these antagonists have any therapeutic efficiency against AHR after long-term H(2)SO(4) inhalation and to elucidate the mechanisms in ovalbumin sensitized guinea pigs.. Specific airway resistance (sRaw), AHR, and BAL fluid were analyzed after an 8-week exposure to H(2)SO(4) aerosol (82 mg/m(3), pH 1.7, 40 mOsm) or hypotonic saline solution (pH 5.9, 40 mOsm) as a control. The H(2)SO(4) group then received a 2-week treatment with FK888, SR48968, or vehicle.. The AHR and the eosinophil count in BAL fluid were significantly increased in the H(2)SO(4) group compared to control animals, while sRaw was significantly elevated in both groups after the 8-week exposure. Treatment with both FK888 and SR48968 significantly reduced the AHR and tended to inhibit eosinophilia in BAL fluid, but sRaw did not change. The degree of AHR improvement with SR48968 was much larger than with FK888.. Our results show that both NK-1 and NK-2 receptor antagonists inhibited long-term H(2)SO(4)-induced AHR in sensitized guinea pigs, and the effect was much greater with an NK-2 antagonist. We suggest that NK-1 or NK-2 antagonism might partially inhibit the H(2)SO(4)-induced influx of eosinophils into the lung.

Topics: Airway Resistance; Animals; Benzamides; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Dipeptides; Eosinophilia; Guinea Pigs; Indoles; Leukocyte Count; Male; Neurokinin-1 Receptor Antagonists; Piperidines; Receptors, Neurokinin-1; Receptors, Neurokinin-2; Sulfuric Acids; Weather

Tachykinins are involved in the development of bronchial inflammation and airway hyperresponsiveness (AHR); however, the role of the neurokinin-1 (NK(1)) receptor in acid-aerosol-induced bronchial impairment in asthmatic patients remains controversial.. To investigate the effects on the NK(1) receptor antagonist FK888 the neurokinin-2 (NK(2)) receptor antagonist SR48968 on sulfuric-acid (H(2)SO(4))-induced AHR in guinea pigs, specific airways resistance (sRaw) and airways responsiveness to methacholine (MCh) were measured before and after 6 h of exposure to H(2)SO(4) aerosol (pH 1.7, 82 mg/m(3)) in ovalbumin-sensitized guinea pigs.. Airway responsiveness to MCh significantly increased (p<0. 05) after the exposure, however sRaw did not. Treatment with FK888 significantly inhibited (p<0.05) H(2)SO(4)-induced AHR in a dose-dependent manner, as did SR48968.. These results suggest that not only NK(2) but also NK(1) receptors might have important roles in the development of acid-aerosol-induced AHR.

Topics: Aerosols; Airway Resistance; Animals; Benzamides; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstriction; Dipeptides; Guinea Pigs; Indoles; Male; Methacholine Chloride; Nebulizers and Vaporizers; Neurokinin-1 Receptor Antagonists; Ovalbumin; Piperidines; Receptors, Neurokinin-2; Sulfuric Acids