Nantenine and papaverine differentially modify synaptosomal membrane enzymes

Summary Papaverine (1-[(3,4-Dimethoxyphenyl) methyl]-6,7-dimethoxyisoquinoline) and nantenine ( O-methyldomesticine ) are chemically related isoquinoline alkaloids displaying similar dose-dependent sedative or convulsant effects, but seem to act differentially on synaptosomal membrane enzymes. Na + , K + -, Mg 2+ -and Ca 2+ -ATPase activities were inhibited by nantenine but not by papaverine, whereas acetylcholinesterase activity remained unchanged by nantenine but slightly enhanced by papaverine. Nantenine inhibited roughly both 20–50% Ca 2+ - and Mg 2+ -ATPase activities but 40–90% Na + , K + -ATPase activity. Kinetic analysis indicated that nantenine interacts with the substrate ATP for Ca 2+ -ATPase activity but that it competes with K + for Na + , K + -ATPase activity. Given the roles of Na + , K + -ATPase and Ca 2+ -ATPase in cation transport and [Ca 2+ ]i regulation, respectively, the inhibitory effect of nantenine upon these enzymes may explain its convulsant effect though not its sedative activity. The sedative action of both nantenine and papaverine is hardly attributable to an effect on the synaptosomal membrane enzymes assayed.