Advenier C, Gnassounou J P, Scarpignato C
Br J Pharmacol. 1987 Mar;90(3):523-30. doi: 10.1111/j.1476-5381.1987.tb11201.x.
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+.
在豚鼠气管和人支气管的离体标本上，测试了三种不同的H2受体拮抗剂（西咪替丁、雷尼替丁和奥美替丁）对乙酰胆碱、组胺和氯化钾（KCl）诱导的收缩的影响。此外，在富含钾的溶液（30 mM）中研究了它们对豚鼠气管螺旋条中钙浓度-反应曲线的影响。最后，在麻醉的豚鼠体内研究了它们对乙酰胆碱和组胺诱导的支气管收缩的作用。在豚鼠离体气管中，奥美替丁——与完全无活性的西咪替丁和雷尼替丁不同——无论刺激物如何，均诱导浓度依赖性舒张：其-log EC50值（即引起50%舒张的负对数浓度）分别为3.46±0.11、4.61±0.09和4.20±0.12，对应于乙酰胆碱、组胺和KCl。在无钙、富含钾的溶液中，该化合物在接近抵消组胺在正常克雷布斯溶液中致痉作用所需浓度时，能够抑制钙诱导的收缩。在人支气管制备物中获得的结果与在豚鼠气管螺旋条中观察到的结果相似。当在体内测试对乙酰胆碱或组胺诱导的支气管收缩的作用时，奥美替丁（静脉注射10和30 mg Kg-1）显著降低了两种药物引起的肺气道阻力（Raw）增加。西咪替丁和雷尼替丁再次完全无效。总之，奥美替丁在豚鼠和人的气道上表现出非特异性的抗痉挛活性。这种作用独立于H2受体阻断，代表了该药物的一种副作用，可能与其对钙内流以及细胞内钙的作用或释放的干扰有关。
