Tulp M T, Zaagsma J
Eur J Pharmacol. 1977 Sep 15;45(2):95-9. doi: 10.1016/0014-2999(77)90078-4.
The time course of the onset and decline of histamine antagonism by 1-(2-(diarylmethoxy)ethyl)aziridines, compounds which could be expected to have H1-receptor alkylating properties, was investigated on the longitudinal muscle strip of the guinea pig ileum. Experiments were performed with normal preparations and with muscle strips pretreated with a prostaglandin synthesis inhibitor in order to prevent spontaneous rise of muscle tone. In contrast to the previously reported observation that antihistaminic potency decreased with prolongation of the preincubation time, histamine antagonism by the aziridine compounds remained at a constant level for more than 60 min in the presence of indomethacin. This indicated that the aziridines are not hydrolyzed either directly in solution or after interaction with the tissue since the supposed hydrolysis product had a significantly lower antihistaminic activity. A comparison between 1-(2-diphenylmethoxy)ethyl)aziridine and diphenhydramine showed the former compound to have a slightly more rapid onset and a considerably more rapid decline of histamine receptor blockade. It was concluded that 1-(2-(diarylmethoxy)ethyl)aziridines did not alkylate the histamine H1-receptor in the longitudinal muscle layer of the guinea pig ileum.
对1-(2-(二芳基甲氧基)乙基)氮丙啶（有望具有H1受体烷基化特性的化合物）组胺拮抗作用的起效和消退的时间进程，在豚鼠回肠纵肌条上进行了研究。实验分别在正常标本以及用前列腺素合成抑制剂预处理过的肌条上进行，以防止肌张力的自发升高。与之前报道的抗组胺效力随预孵育时间延长而降低的观察结果相反，在吲哚美辛存在的情况下，氮丙啶化合物的组胺拮抗作用在60多分钟内保持恒定水平。这表明氮丙啶无论是在溶液中直接水解，还是与组织相互作用后都不会水解，因为假定的水解产物具有明显较低的抗组胺活性。1-(2-二苯基甲氧基)乙基)氮丙啶和苯海拉明之间的比较表明，前一种化合物组胺受体阻断的起效略快，消退则快得多。得出的结论是，1-(2-(二芳基甲氧基)乙基)氮丙啶不会使豚鼠回肠纵肌层中的组胺H1受体烷基化。
