title: Behavioral effects of (-)10,11-methylenedioxy-N-n-propylnoraporphine, an orally effective long-acting agent active at central dopamine receptors, and analogous aporphines.
abstract: Substituted and unsubstituted 10,11-methylenedioxy derivatives of apomorphine (APO) or its N-propyl congener (NPA) were synthesized and evaluated for their ability to alter motor activity or to induce stereotyped behavior in the rat. Of these, (-)10,11-methylenedioxy-N-n-propylnoraporphine hydrochloride (MDO-NPA) was the most active, and the only compound which was found to be active after oral administration. Also, MDO-NPA was more potent than NPA or APO in producing stereotypy, but large doses of these three aporphines were equipotent in stimulating motor activity. The duration of action of MDO-NPA exceeded that of NPA and APO, and increased with increasing doses. The effects of MDO-NPA on general activity were biphasic: larger doses stimulated activity: smaller doses markedly inhibited it and induced catalepsy. Catalepsy did not occur with NPA or APO and their motor-inhibitory effects were apparent only in aroused rats. The stereotypic effects of MDO-NPA were blocked by small doses of haloperidol, but not by large doses of reserpine. The effects due to large or small doses of MDO-NPA were also blocked by a microsomal enzyme inhibitor which did not interfere with the actions of NPA. These results suggest that MDO-NPA is a long-acting, orally effective prodrug of NPA with depot properties and dose-dependent agonistic and antagonistic interactions with central dopamine-mediated systems.
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D011954:Receptors, Dopamine; C009074:N-n-propylnorapomorphine; C033829:10,11-methylenedioxy-N-propylnoraporphine; D011335:Proadifen; D001058:Apomorphine