In vitro inhibition of cyclic 3' 5',-AMP-phosphodiesterase by a group of structural analogues of glaucine.

Both glaucine and six of its structural analogues applied in increasing concentrations produced a concentration-dependent inhibiton of cyclic 3' 5'-AMP-phosphodiesterase in homogenates from different organs of guinea-pigs and rats. At one and the same concentration of the compound tested the percentage of inhibition varied within wide ranges depending on the compound used, as well as on the organ and on the Km of phosphodiesterase. The changes in the chemical structure of glaucine and the changes in the inhibitory effects on phosphodiesterase activity of tissue homogenates were compared. Some of the compounds applied in appropriate concentrations showed a twice higher inhibitory activity than glaucine. This finding is of particular importance having the mind the much lower toxicity of these compounds compared with glaucine. Essential differences in the dynamics of the concentration-dependent phosphodiesterase inhibition between the compounds were established. The observed peculiarities of the inhibitory effects of the compounds tested favour the concept of the multiple nature of phosphodiesterase. The data from the pharmacological investigation on glaucine and its semisynthetic analogues led us to believe that the effect of 2 compound on phosphodiesterase activity of homogenates from intestinal smooth muscles does not justify any definitive conclusions about the character of its effect on the smooth-muscle activity.