Comparison of the dopaminergic effects of apomorphine and (-)-N-n-propylnorapomorphine.

(-)-N-n-propylnorapomorphine (NPA) was found to be 2.3 times more active than apomorphine in producing stereotypy in novice mice. This potency ratio was not changed by reserpine pretreatment (4 h prior). However, when mice pretreated with reserpine 24 h earlier were used, NPA was found to be 6.5 times more active in producing locomotor stimulation and 8.7 times more active in producing stereotypy than apomorphine. In these mice, a second dose of reserpine or alpha-methyl-p-tyrosine (alphaMT) given 4 h prior to NPA administration considerably reduced the locomotor effects of NPA. Such treatments did not modify the effects of apomorphine. Phenoxybenzamine failed to alter the responses of both these drugs. It was concluded that, while apomorphine possesses direct dopamine (DA) receptor stimulant effect, that of NPA is partly direct and partly indirect in nature. In novice mice, NPA was 91 times more active than apomorphine in inhibiting the alphaMT-induced depletion of brain DA. The question is raised why the powerful DA receptor agonistic effect of NPA did not produce equivalent behavioral responses in mice. The likely explanation would be that, in addition to its effect on the striatonigral DA system from which the stereotypic response originates, NPA also exerts a predominant effect on the mesolimbic areas. The combined effect of NPA on these two components of the DA system is reflected in the biochemical results. The overall dopaminergic effect of NPA is several times greater than that of apomorphine.