cinnarizine and Asthma

Topics: Animals; Asthma; Bronchi; Bronchodilator Agents; Calcium; Calcium Channel Blockers; Cell Adhesion; Cinnarizine; Dogs; Guinea Pigs; Histamine Release; Humans; Ion Channels; Mast Cells; Muscle, Smooth; Nifedipine; Physical Exertion; Sheep; Verapamil

The intracellular concentration of free Ca2+ ions regulates many functions of cells including secretion, contraction, transport processes, and motility, among others. All of the pathogenetic processes in asthmatic airways are Ca2+-dependent phenomena: excitation-contraction coupling in smooth muscle, stimulus-secretion coupling in mast cells and mucous glands, nerve impulse initiation and conduction, and the development of inflammatory infiltration. Ca2+ entry blockers such as nifedipine and verapamil may affect exercise-induced asthma, airway tone, mast cell mediator release, and experimental anaphylaxis. Calmodulin-active drugs can inhibit smooth muscle contraction and mediator release. A new generation of Ca2+ antagonists may find a role in the management of asthma.

Topics: Asthma; Asthma, Exercise-Induced; Autacoids; Binding Sites; Calcium; Calcium Channel Blockers; Calmodulin; Cinnarizine; Cromolyn Sodium; Epinephrine; Female; Humans; Inflammation; Ion Channels; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Neutrophils; Theophylline

1 Cinnarizine, an inhibitor of calcium ion transport across smooth muscle cell membrane, has been shown to exert an anti-asthmatic effect in patients with chronic asthma. 2 It is postulated that antagonism to calcium ion transport across the mast cell membrane may cause the compound to have a pharmacological effect similar to sodium cromoglycate. 3 Cinnarizine is orally active and its therapeutic effect is demonstrated in a double-blind, cross-over, placebo controlled study. 4 Patient benefit was shown by a significant improvement in peak flow rate. A non-significant trend towards a reduction in symptomatic bronchodilator usage and a decrease in asthma symptom score was also shown. 5 It is concluded that cinnarizine could well prove to be the first of a new family of anti-asthmatic drugs offering a protective effect when taken systemically.

Topics: Adult; Asthma; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Humans; Male; Middle Aged; Piperazines; Placebos

Calcium influx, inflammatory infiltration, cytokine production, immunoglobulin E activation and oxidative stress play coordinated roles in bronchial asthma pathogenesis. We aim to assess the protective effect of cinnarizine against experimentally induced bronchial asthma.. Bronchial asthma was induced by ovalbumin sensitization and challenge. Rats were allocated into a normal control, an asthma control, a dexamethasone (standard) treatment, and 2 cinnarizine treatment groups. The respiratory functions tidal volume (TV) and peak expiratory flow rate (PEFR), the inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-5 (IL-5) in lung tissue, the allergic immunoglobulin IgE in serum, the absolute eosinophil count (AEC) in bronchoalveolar lavage fluid (BALF), as well as the oxidative and nitrosative markers glutathione reduced (GSH) and superoxide dismutase (SOD) in lung tissue and nitric oxide end products (NOx) in BALF were assessed, followed by a histopathological study.. Cinnarizine administration significantly restored TV, PEFR, TNF-α, IL-5, IgE, AEC, GSH, SOD and NOx values back to normal levels, and significantly decreased perivascular and peribronchiolar inflammatory scores.. Cinnarizine may protect against experimental bronchial asthma. Suppressant effect of cinnarizine on pro-inflammatory cytokines release, IgE antibody production, eosinophil infiltration as well as oxidative and nitrosative stress may explain its anti-asthmatic potential.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Bronchoalveolar Lavage Fluid; Cinnarizine; Cytokines; Dexamethasone; Interleukin-5; Lung; Male; Nitric Oxide; Ovalbumin; Oxidative Stress; Peak Expiratory Flow Rate; Rats; Reactive Nitrogen Species; Tidal Volume; Tumor Necrosis Factor-alpha