Bretz U, Martin U, Mazzoni L, Ney U M
Eur J Pharmacol. 1983 Jan 21;86(3-4):321-8. doi: 10.1016/0014-2999(83)90180-2.
A strong, long-lasting and reproducible tachyphylaxis was produced in rats by implantation of osmotic minipumps delivering isoprenaline continuously. The degree of tachyphylaxis was determined by measuring the inhibitory effect of isoprenaline on the passive cutaneous anaphylaxis (PCA). One dose of ketotifen given 1 h before the PCA test reversed this in vivo tachyphylaxis, as did dexamethasone given 24 h earlier. Implantation of a second minipump containing ketotifen prevented the development of tachyphylaxis. Weak tachyphylaxis was induced in guinea-pig trachea in vitro by incubation with a high concentration of isoprenaline, the effect being estimated by measuring the relaxation of carbachol-contracted trachea. Ketotifen partially restored the sensitivity of the trachea but this was considered to be a direct potentiation of isoprenaline effects rather than a reversal of tachyphylaxis since the same effect was seen in non-pretreated trachea. It is thought that the reversal of experimental beta-adrenergic tachyphylaxis by ketotifen could have implications for its use in the prophylactic treatment of asthma.
通过植入持续输送异丙肾上腺素的渗透微型泵，在大鼠中产生了强烈、持久且可重复的快速耐受性。通过测量异丙肾上腺素对被动皮肤过敏反应（PCA）的抑制作用来确定快速耐受性的程度。在PCA试验前1小时给予一剂酮替芬可逆转这种体内快速耐受性，提前24小时给予地塞米松也有同样效果。植入第二个含有酮替芬的微型泵可防止快速耐受性的发展。在体外，通过与高浓度异丙肾上腺素孵育，在豚鼠气管中诱导出微弱的快速耐受性，通过测量卡巴胆碱收缩气管的舒张来评估其效果。酮替芬部分恢复了气管的敏感性，但这被认为是对异丙肾上腺素作用的直接增强，而不是快速耐受性的逆转，因为在未预处理的气管中也观察到了相同的效果。据认为，酮替芬对实验性β-肾上腺素能快速耐受性的逆转可能对其在哮喘预防性治疗中的应用有影响。
