In vitro and in vivo inhibitory effects of propentofylline on cyclic AMP phosphodiesterase activity.

1-(5'-Oxohexyl)-3-methyl-7-propylxanthine (propentofylline), a vasoactive agent, was investigated for its in vitro and in vivo inhibitory effects on cyclic AMP phosphodiesterases activity. Soluble cyclic AMP phosphodiesterases from the cerebral cortex, heart muscle, descending aorta and platelet showed two Km values, high and low. The low Km values were in the range of 2.1-3.0 mumol/l and the high Km values were 111, 28.7, 30.2 and 18.7 mumol/l, respectively. Propentofylline inhibited the enzyme from the 4 tissues noncompetitively. Ki values for the low and high Km cyclic AMP phosphodiesterases were 83.4-135 and 107-188 mumol/l, respectively. In the four tissues, the enzyme inhibitory effect of propentofylline was 1/4 to 1/10 times that of 3-isobutyl-1-methylxanthine (IBMX) but 3-9 and 6-17 times as potent as those of theophylline and caffeine, respectively. The in vivo cyclic AMP phosphodiesterase inhibitory effect of propentofylline was determined in mice using an elevation of plasma cyclic AMP levels as a measure. When given both singly and in combination with isoprenaline (isoproterenol), propentofylline was a potent inhibitor of cyclic AMP phosphodiesterase in the case of intravenous administration.