Repetyeva O. Antihypoxic, antioxidant and antiexudative properties of spirocyclic oxoindolic derivates of 2-amino-4H-pyran - structural analogues of melatonin

Thesis is devoted the search of potential antihypoxants with antioxidant and antiexudative properties in the range of 15 spirocyclic oxoindolic derivates of 2-amino-4H- pyran - structural analogues of melatonin. We have established the dependence in the the range of spirocyclic oxoindolic derivates of 2-amino-4H- pyran. LD50 spirazydol is the most active substance for intragastric administration to mise and rats makes 1800 mgs/kg and 1583,3 mgs/kg, accordingly. ED50 for intragastric introduction rats - 18,6 mgs/kg. Spirazydol in the dose of ЕD50 at non-permanent prophylactic introduction in the conditions of hematic, normobaric, hypobaric and histotoxic hypoxia (white mise) prolongs life to animals in 1,97; 2,1; 2,5 and 3,28 times accordingly, and Spirazydol does not yield to preparation of comparison of Mexidol. In addition, in the conditions of in vitro Spirazidоl is characterized by high antiradical and antioxidant activity. Properties of spirazydol (antihypoxic and antioksidant) are confirmed on the models of tetrachlormethanoic hepatitis for mise and for rats and myocarditis caused isadrin for rats. Spirazydol reduces content of TBK-reactants, promotes the level of reduced glutathione in relation to hepatitis without treatment, positively influences on the index of mass coefficient of liver and prolongs life for rats. In rats with experimental myocarditis caused isadrin spirazydol (into a stomach in a dose 18,6 mgs/kg) normalizes electrocardiography; considerably ar-rests the formation both of primary and secondary products of free-radical oxidation.