Kornienko V. A search and development of mean is for the pharmacological correction of nefro- and kardiopatiy among n-c8-zamischenikhi of the condensed derivates of ksantinu

The thesis is devoted to the screening and the establishment of the "structure- activity" relationship of a new series of organic compounds - N-C8-substituted and condensed xanthine derivatives. Benfuram's LD50 (the most active substance), while intraperitoneal administration to mice and rats was 750.0 ± 45.68 mg / kg and 1250.0 ± 46.29 mg / kg respectively. ED50 is equal to 30.0 ± 0.24 mg / kg while intragastric administration to rates. In chronic experiment, it was found, that benfuram affects not adversely on the function of vital organs and systems of rats. On benfuram's example, it was proved, that mechanisms of diuretic effect of N-C8-substituted and condensed xanthine derivatives are caused by: an increase in glomerular filtration rate; inhibition of aldosterone secretion; a caution of antidiuretic effects of mineralocorticoids in a joint application with spironolactone associated with the normalization of water-salt metabolism; the relaxation of the vascular wall that leads to increased diuretic effect. Hypotensive effect of benfuram was confirmed in acute experiments on rabbits. It was found, that the place of benfuram's diuretic effect localization is both the distal and proximal parts of the convoluted tubules of the nephron.