piperidines and Bronchitis

The medical and social impact of cough is substantial. Current antitussive agents at effective doses have adverse events such as drowsiness, nausea and constipation that limit their use. There is also recent evidence that standard antitussive agents, such as codeine, may not reduce cough during upper respiratory infections. Therefore, there is a need for more effective and better-tolerated agents. The efficacy of levocloperastine, a novel antitussive, which acts both centrally on the cough center and on peripheral receptors in the tracheobronchial tree in treating chronic cough, was compared with that of other standard antitussive agents (codeine, levodropropizine and DL-cloperastine) in six open clinical trials. The studies enrolled patients of all ages with cough associated with various respiratory disorders including bronchitis, asthma, pneumonia and chronic obstructive pulmonary disease. Levocloperastine significantly improved cough symptoms (intensity and frequency of cough) in all trials, and improvements were observed after the first day of treatment. In children, levocloperastine reduced nighttime awakenings and irritability, and in adults it was effective in treating cough induced by angiotensin-converting enzyme inhibitors. When compared with other antitussive agents, levocloperastine had improved or comparable efficacy, with a more rapid onset of action. Importantly, no evidence of central adverse events was recorded with levocloperastine, whereas drowsiness was reported by a significant number of patients receiving codeine. Levocloperastine is an effective antitussive agent for the treatment of cough in patients of all ages. It has a more rapid onset of action than standard agents with an improved tolerability profile.

Topics: Adolescent; Adult; Aged; Antitussive Agents; Bronchitis; Chronic Disease; Clinical Trials as Topic; Codeine; Cough; Female; Humans; Lung Diseases; Male; Middle Aged; Patient Selection; Piperidines; Propylene Glycols; Stereoisomerism; Treatment Outcome

Topics: Acute Disease; Antitussive Agents; Bronchitis; Child; Child, Preschool; Clinical Trials as Topic; Cough; Double-Blind Method; Female; Humans; Male; Piperidines; Random Allocation

The results of 6 clinical trials involving a total of 174 patients are reported. Levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526) was compared in double-blind manner with placebo, morclofone and cloperastine. The antitussive activity and therapeutic efficacy of the drug were shown to be greater than those of placebo and morclofone and similar to those of cloperastine. Levodropropizine was effective in about 80% of patients; in responders, cough frequency was reduced by an average of 33-51%. Levodropropizine was generally well tolerated and mild side-effects were reported for only 3% of patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antitussive Agents; Benzophenones; Bronchitis; Clinical Trials as Topic; Cough; Double-Blind Method; Drug Tolerance; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Piperidines; Propylene Glycols

Topics: Adolescent; Adult; Aged; Asthma; Bronchitis; Capsules; Clinical Trials as Topic; Double-Blind Method; Histamine H1 Antagonists; Humans; Ketotifen; Middle Aged; Piperidines; Placebos; Tablets; Thiophenes; Time Factors

A randomized multicentre trial was done to investigate the protective effects of ketotifen and disodium cromoglycate (DSCG) in the therapy of bronchial asthma. 236 patients with seasonal asthmatic symptoms were treated and controlled in the summer of 1978. Both drugs showed a significant improvement of the lung function and a marked reduction of asthmatic symptoms, cough and expectoration.

Topics: Adrenergic beta-Agonists; Asthma; Beclomethasone; Bronchitis; Clinical Trials as Topic; Cromolyn Sodium; Histamine H1 Antagonists; Humans; Ketotifen; Piperidines; Random Allocation; Seasons; Spirometry; Theophylline; Thiophenes

In a double-blind long-term study, regular inhalations of a short-acting selective beta2-stimulator, rimiterol, was compared with a long-acting one, terbutaline. The trial comprised 60 patients with chronic obstructive lung disease, all patients were on a small dose of an oral beta2-stimulator. Both drugs were regularly given in aerosol form with a minimum dose of three inhalations three times daily. The main purpose was to study subjective and objective side effects. Haematological, hepatic and renal functions were screened for toxicity. Consumption of spray was recorded. No side effects occurred. There was no evidence of development of isoprenaline resistance. The consumption of spray was the same in both groups. In this study, regular inhalation treatment of rimiterol seemed to be as effective as terbutaline in long-term bronchodilator therapy.

Topics: Aerosols; Asthma; Bronchitis; Catechols; Chronic Disease; Drug Evaluation; Female; Humans; Isoproterenol; Lung Diseases, Obstructive; Male; Piperidines; Pulmonary Emphysema; Terbutaline

A comparison between the acute effects of rimiterol (0.5 mg) and salbutamol (0.2 mg.) has been made using metered dose aerosols. In this dosage it was found that the peak effect of the two drugs was the same but that the effect of rimiterol was less prolonged than that of sulbutamol. No increase in blood pressure occurred and heart rate changes were minimal after both drugs. Rimiterol is an acceptable alternative to the short-acting isoprenaline but lacks the cardiovascular effects of isoprenaline and is an alternative to salbutamol where very prolonged action is unnecessary.

Topics: Adult; Aerosols; Airway Obstruction; Albuterol; Asthma; Blood Pressure; Bronchi; Bronchitis; Bronchodilator Agents; Cardiovascular System; Catechols; Dose-Response Relationship, Drug; Female; Heart Rate; Humans; Isoproterenol; Male; Methanol; Middle Aged; Piperidines; Respiratory Function Tests; Respiratory Therapy

Topics: Analysis of Variance; Antitussive Agents; Bronchitis; Chronic Disease; Cough; Densitometry; Humans; Oxazines; Piperidines; Placebos; Sputum; Viscosity

1. Several observations suggest that tachykinins are involved in the pathogenesis of bronchopulmonary alterations. We have investigated the effect of antagonists for tachykinin NK1 (SR 140333), NK2 (SR 48968) or NK3 (SR 142801) receptors on inflammatory cell recruitment, tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 release and matrix metalloproteinase (MMP)-9 activity in the bronchoalveolar lavage fluid (BALF) of mice exposed to lipopolysaccharide (LPS; 100 microg/mL aerosol for 30 min). 2. Treatment of mice with a combination of SR 140333 and SR 48968 (10(-6) mol/L, aerosol) significantly reduced the increase in the number of total cells and neutrophils and MMP-9 activity in the BALF of mice 2.5 h after LPS exposure. Treatment with the NK3 antagonist SR 142801 (10(-6) mol/L, aerosol) did not inhibit the influx of neutrophils, but markedly reduced the increase in TNF-alpha and IL-6 levels at 2.5 h and MMP-9 activity at 20 h. 3. These results show that the three tachykinin receptor antagonists may interfere with the development of airway inflammation, namely neutrophilia, TNF-alpha release or MMP-9 activity in the BALF of mice exposed to LPS and suggest that not only NK1 and NK2 receptors, but also NK3 receptors are involved in the modulation of the inflammatory response and airway remodelling.

Topics: Aerosols; Animals; Benzamides; Bronchitis; Bronchoalveolar Lavage Fluid; Interleukin-6; Lipopolysaccharides; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Neurokinin-1 Receptor Antagonists; Piperidines; Pulmonary Alveoli; Quinuclidines; Receptors, Neurokinin-2; Receptors, Neurokinin-3; Time Factors; Tumor Necrosis Factor-alpha

Using a guinea pig model of allergic asthma, we investigated the effects of the inhaled, highly selective nonpeptide tachykinin NK1 and NK2 receptor antagonists SR 140333 and SR 48968, respectively, on allergen-induced early (EAR) and late (LAR) asthmatic reactions, airway hyperreactivity (AHR) after these reactions, and infiltration of inflammatory cells in the airways. Both SR 140333 (100 nM, 3 min) and SR 48968 (100 nM, 3 min) had no effect on the severity of the EAR, while the NK2 receptor antagonist SR 48968, but not the NK1 receptor antagonist SR 140333, caused significant inhibition of the LAR. SR 140333 significantly reduced the allergen-induced AHR to histamine, both after the EAR and the LAR. By contrast, SR 48968 did not affect the AHR after the EAR, but significantly attenuated the AHR after the LAR. Bronchoalveolar lavage studies performed after the LAR indicated that SR 140333 caused significant inhibition of allergen-induced infiltration of eosinophils, neutrophils and lymphocytes, while SR 48968 attenuated the infiltration of neutrophils and lymphocytes, but not of eosinophils. Both NK receptor antagonists tended to reduce the accumulation of ciliated epithelial cells in the airways. These results indicate that NK1 and NK2 receptors are importantly, but differentially, involved in the development of allergen-induced airways obstruction, AHR and infiltration of inflammatory cells in the airways. Therefore, both NK1 and NK2 receptor antagonists, or dual NK1 and NK2 antagonists, could be useful in the treatment of allergic asthma.

Topics: Allergens; Animals; Asthma; Benzamides; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchitis; Chemotaxis, Leukocyte; Eosinophils; Guinea Pigs; Lymphocytes; Neurokinin-1 Receptor Antagonists; Neutrophils; Ovalbumin; Piperidines; Quinuclidines; Receptors, Neurokinin-1; Receptors, Neurokinin-2

Bronchial lability was measured in 10 normal subjects, 33 typical asthmatics, and 23 smokers with ventilatory defect, by three different methods in the course of a week. There was little difference between exercise/bronchodilator lability index, spontaneous diurnal variation, and histamine challenge in detecting bronchial lability. It was possible that histamine challenge was more sensitive and more specific to asthma. It is recommended that this test is used first in studies to detect bronchial lability but those apparently normal should also be tested by the other methods. There was no correlation between the numerical value of these indices of broncholability in abnormal subjects. The asthmatic and bronchitic subjects were not separated by any of the three methods.

Topics: Adult; Airway Resistance; Asthma; Bronchial Provocation Tests; Bronchitis; Chronic Disease; Circadian Rhythm; Exercise Test; Forced Expiratory Volume; Humans; Middle Aged; Peak Expiratory Flow Rate; Piperidines; Smoking

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Anti-Bacterial Agents; Antitussive Agents; Bronchitis; Expectorants; Histamine H1 Antagonists; Humans; Ketotifen; Parasympatholytics; Physical Therapy Modalities; Piperidines; Thiophenes; Xanthines

Topics: Acetylcholine; Adolescent; Adult; Aged; Androstanes; Anesthesia, General; Asthma; Bromides; Bronchi; Bronchitis; Child; Child, Preschool; Cholinesterases; Female; Humans; Liver Diseases; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Piperidines; Spirometry

Topics: Alkaloids; Bronchitis; Chromatography; Diarrhea; Dysentery; Infrared Rays; Optical Rotation; Piperidines; Plant Extracts; Plants; Quinolizines; Spectrum Analysis; Syphilis; Ultraviolet Rays

Topics: Adult; Aged; Antitussive Agents; Bronchiectasis; Bronchitis; Bronchopneumonia; Cough; Female; Humans; Hypertension, Pulmonary; Lung Neoplasms; Male; Middle Aged; Piperidines; Tracheitis

Topics: Abdomen; Adult; Analgesics; Anesthesia, Endotracheal; Bronchitis; Female; Humans; Lung Diseases; Piperidines; Postoperative Complications; Tracheal Diseases

Topics: Bronchitis; Chronic Disease; Humans; Injections, Intravenous; Khellin; Lung Diseases; Lung Diseases, Obstructive; Phenothiazines; Piperidines; Posture; Quaternary Ammonium Compounds; Respiratory Tract Diseases; Theophylline

Topics: Antitussive Agents; Bronchitis; Bronchoscopy; Chronic Disease; Cough; Humans; Piperidines; Tuberculosis; Xanthenes

Topics: Alkaloids; Asthma; Bronchitis; India; Medicine, Ayurvedic; Piperidines

Topics: Anti-Allergic Agents; Asthma; Bronchitis; Drug Therapy; Histamine H1 Antagonists; Piperidines; Respiratory Insufficiency; Thioxanthenes