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  • Title: Relaxant effect of the H2-receptor antagonist oxmetidine on guinea-pig and human airways.
    Author: Advenier C, Gnassounou JP, Scarpignato C.
    Journal: Br J Pharmacol; 1987 Mar; 90(3):523-30. PubMed ID: 2882803.
    Abstract:
    The effects of three different H2-receptor antagonists (cimetidine, ranitidine and oxmetidine) were tested on isolated preparations of guinea-pig trachea and human bronchus against contractions induced by acetylcholine, histamine and potassium chloride (KCl). In addition, their influence on calcium concentration-response curves in guinea-pig tracheal spirals was examined in a potassium-rich solution (30 mM). Finally, their effects were studied in vivo against acetylcholine and histamine-induced bronchoconstriction in anaesthetized guinea-pigs. In guinea-pig isolated trachea, oxmetidine--in contrast to cimetidine and ranitidine, which were completely inactive--induced a concentration-dependent relaxation regardless of the excitatory stimulus: its--log EC50 values (i.e. the negative log concentration that caused a 50% relaxation) were 3.46 +/- 0.11, 4.61 +/- 0.09 and 4.20 +/- 0.12 against acetylcholine, histamine and KCl, respectively. In Ca2+-free, K+-enriched solution, the compound was able to inhibit Ca2+-induced contractions at concentrations close to those needed to counteract the spasmogenic effect of histamine in normal Krebs solution. Results obtained in the human bronchus preparation were similar to those observed in guinea-pig tracheal spirals. When tested against acetylcholine or histamine-induced bronchoconstriction in vivo, oxmetidine (10 and 30 mg Kg-1 intravenously) significantly reduced the increase in pulmonary airway resistance (Raw) induced by both agents. Once again, cimetidine and ranitidine were completely ineffective. In summary, oxmetidine displayed non-specific antispasmogenic activity on guinea-pig and human airways. This effect, which is independent of H2-receptor blockade, represents a side-effect of the drug which may be connected to its interference with Ca2+ influx and the action or release of intracellular Ca2+.
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