Iovcheva G, Staneva-Stoĭcheva D
Eksp Med Morfol. 1979;18(2):86-92.
The authors carried out studies on cats, guinea pigs, rats and mice, using isolated smooth muscle organs (bronchi, ileum of guinea pig), and examined bronchodilatating, diuretic, antihistaminic action and acute toxiticy of three N-basic substituted derivatives of 1,3-dimethiylxanthine (theophyline) namely: 7-bis-(2-hydroximethyl)-amino-ethyl theophyline under the form of a base (compound G111, tartarate (G112) and nicotinate (G113). The studies were performed in comparison with theophyline. It was found that the substance G113 had a considerable bronchodilatating effect, surpassing in strength and velocity that of theophyline. The examined substances had antihistaminic effect of G113 as the antihistaminic effect of G113 surpassed that of theophyline under experimental conditions in vivo. It was established that all three compounds manifested diuretic activity close to that of theophyline. The derivatives of theophyline, examined by us, had considerably lower toxicity (7,17, resp. 8 times) than that of theophyline. On the basis of the experimental results and some advantages of the examined compounds (good solubility, low toxicity) perspectives are seen for their eventual clinical trial as bronchodilatating and diuretic drugs.
作者使用离体平滑肌器官（支气管、豚鼠回肠）对猫、豚鼠、大鼠和小鼠进行了研究，并检测了1,3 - 二甲基黄嘌呤（茶碱）的三种N - 碱性取代衍生物，即碱形式的7 - 双 -（2 - 羟甲基）- 氨基 - 乙基茶碱（化合物G111）、酒石酸盐（G112）和烟酸盐（G113）的支气管扩张、利尿、抗组胺作用及急性毒性。研究是与茶碱对比进行的。发现物质G113具有相当大的支气管扩张作用，在强度和速度上超过茶碱。所检测的物质具有抗组胺作用，其中G113的抗组胺作用在体内实验条件下超过茶碱。已确定所有三种化合物表现出的利尿活性与茶碱相近。我们所检测的茶碱衍生物的毒性比茶碱低得多（分别低7倍、17倍和8倍）。基于实验结果以及所检测化合物的一些优点（良好的溶解性、低毒性），有望最终将它们作为支气管扩张和利尿药物进行临床试验。
