Tissue levels of N-n-propylnorapomorphine after treatment with (-)10,11-methylenedioxy-N-n-propylnoraporphine, an orally long-acting prodrug active at central dopamine receptors.

High performance liquid chromatography with electrochemical detection was used to assay N-n-propylnorapomorphine (NPA) and other aporphines. Pretreatment of rats with (-)10,11-methylenedioxy-N-n-propylnoraporphine (MDO-NPA) yielded dose-dependent increases in tissue levels of NPA after oral or parenteral administration. Cerebral levels of NPA significantly paralleled the stereo-typed behavioral effects produced by MDO-NPA at several doses and times. Pretreatment with the microsomal oxidase inhibitor SKF-525A (see Methods) prevented these behavioral effects of MDO-NPA and blocked the formation of NPA in vitro. These results support the suggestion that MDO-NPA is a uniquely orally effective and relatively long-acting aporphine which acts at cerebral dopamine receptors as a prodrug of NPA.