[Pharmacological activity of N-basic substituted derivatives of 1,3-dimethylxanthine]

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.