Effect of papaverine analogues on 3', 5'-adenosine monophosphate phosphodiesterase activity in rat brain

In vitro studies were carried out of some hydrated papaverine analogues on the rat cerebral phosphodiesterase (PD). The potential inhibitory effect of the newly-synthesized drugs (Trifonov, Orahovats, 1978), as well as the effect of papaverine, were studied in a series of concentrations (1 micrometer to 100 micrometers) on brain homogenates. The enzyme activity was determined by the isotope method of Filburn and Karn (1972) at two substrate concentrations (1 and 200 micrometers). Dihydropapaverine was found to have practically no effect. 6'-Iodo-dihydropapaverine is a weaker inhibitor of the enzyme with low Km, compared with 6'-bromo-dihydropapaverine, however, unlike it its effect on PD with high Km is more marked. Among the compounds tested, papaverine is the most powerful inhibitor of the enzyme with low and high Km. The kinetic analysis of PD with low and with high Km, performed after Lineweaver and Burk, has shown hat the inhibition of the enzyme by the studied substance is reversable and of the competitive type. The inhibitory constants of the compounds studied were estimated.