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.
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D001060:Aporphines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects
D001060:Aporphines; D011954:Receptors, Dopamine; C009074:N-n-propylnorapomorphine; C033829:10,11-methylenedioxy-N-propylnoraporphine; D001058:Apomorphine