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Relaxant effect of the H 2 ‐receptor antagonist oxmetidine on guinea‐pig and human airways
Author(s) -
Advenier Charles,
Gnassounou Jean Pierre,
Scarpignato Carmelo
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb11201.x
Subject(s) - guinea pig , antagonist , pharmacology , medicine , receptor , chemistry
1 The effects of three different H 2 ‐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. 2 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 EC 50 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 Ca 2+ ‐free, K + ‐enriched solution, the compound was able to inhibit Ca 2+ ‐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. 3 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 ( R aw ) induced by both agents. Once again, cimetidine and ranitidine were completely ineffective. 4 In summary, oxmetidine displayed non‐specific antispasmogenic activity on guinea‐pig and human airways. This effect, which is independent of H 2 ‐receptor blockade, represents a side‐effect of the drug which may be connected to its interference with Ca 2+ influx and the action or release of intracellular Ca 2+ .