Behavioral effects of (-)10,11-methylenedioxy-N-n-propylnoraporphine, an orally effective long-acting agent active at central dopamine receptors, and analogous aporphines.

A Campbell, R J Baldessarini, V J Ram, J L Neumeyer

Index: Neuropharmacology 21(10) , 953-61, (1982)

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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.