A comparative study of two parasympatholytic bronchodilator agents: ipratropium bromide and diphemanil methylsulfate.
Ipratropium and diphemanil are synthetic quaternary ammonium compounds with antimuscarinic properties. By using in vitro measurements of tension changes in isolated guinea-pig trachealis muscle strips and in vivo measurements of lung mechanics changes in anesthetized, vagotomized cats, the two drugs were compared in terms of their relative bronchodilator potency, mode of action and apparent site of activity in the bronchial tree. Ipratropium and diphemanil were about equipotent in antagonizing airway smooth muscle contraction induced by the cholinergic agonists, methacholine (in vitro) and carbachol (in vivo). When noncholinergic stimulation was used to augment smooth muscle tone, i.e., hypertonic potassium in the isolated preparations and serotonin in the vagotomized animals, only diphemanil exhibited significant bronchodilator activity. Simultaneous measurements of pulmonary resistance and dynamic compliance were used to partition in vivo bronchodilator effects between large and small airways. The parasympatholytic bronchodilator effects of both drugs were distributed uniformly along the bronchial tree, whereas the direct spasmolytic action of diphemanil appeared to manifest itself preferentially on large airways.[1]References
- A comparative study of two parasympatholytic bronchodilator agents: ipratropium bromide and diphemanil methylsulfate. Diamond, L., O'Donnell, M. J. Pharmacol. Exp. Ther. (1981) [Pubmed]
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