Loftus B G, Price J F, Heaton R, Costello J F
Clin Allergy. 1985 Sep;15(5):465-71. doi: 10.1111/j.1365-2222.1985.tb02296.x.
We have studied the effects of Ketotifen [Ke] (10(-4)M and 10(-6)M) on two in vitro models of bronchoconstriction: actively sensitized guinea-pig trachea (GPT), and passively sensitized human bronchial muscle (HBM). Experiments were performed on matched pairs of tissues. Cumulative dose response curves [CDRC] for histamine and acetyl choline were constructed, and repeated after pre-incubation with Ke or saline control. The effect of Ke on maximal antigen induced contractions was also studied. Contraction of GPT by histamine and acetyl choline was inhibited by Ke 10(-4)M, though this effect was not apparent at high doses of acetyl choline. Ke 10(-6)M had a weaker inhibitory effect on histamine and acetyl choline induced responses. Contraction of GPT by antigen was unaffected by Ketotifen. In the HBM model, Ke 10(-4)M inhibited acetyl choline and antigen induced responses. Ketotifen, 10(-6)M had an inhibitory effect on acetyl choline induced contractions, though this was small, and not seen at higher agonist doses. Contraction of HBM by antigen was unaffected by Ke 10(-6)M. We were unable to obtain reproducible CD RC's to histamine with HBM. The weaker or absent effects of Ke 10(-6)M, a level close to that obtained in clinical practice, may explain some of the poor results of clinical trials, and suggest that efficacy may be improved by the use of higher doses.
我们研究了酮替芬Ke对两种支气管收缩体外模型的作用：主动致敏豚鼠气管(GPT)和被动致敏人支气管肌肉(HBM)。实验在配对的组织上进行。构建了组胺和乙酰胆碱的累积剂量反应曲线[CDRC]，并在与Ke或生理盐水对照预孵育后重复进行。还研究了Ke对最大抗原诱导收缩的作用。10⁻⁴M的Ke可抑制组胺和乙酰胆碱引起的GPT收缩，尽管在高剂量乙酰胆碱时这种作用不明显。10⁻⁶M的Ke对组胺和乙酰胆碱诱导的反应具有较弱的抑制作用。抗原引起的GPT收缩不受酮替芬影响。在HBM模型中，10⁻⁴M的Ke可抑制乙酰胆碱和抗原诱导的反应。10⁻⁶M的酮替芬对乙酰胆碱诱导的收缩有抑制作用，尽管作用较小，且在较高激动剂剂量下未观察到。10⁻⁶M的Ke不影响抗原引起的HBM收缩。我们无法在HBM上获得可重复的组胺CDRC。10⁻⁶M的Ke作用较弱或无作用，该水平接近临床实际获得的水平，这可能解释了一些临床试验效果不佳的原因，并表明使用更高剂量可能会提高疗效。
