S(+)Apomorphines. Selective inhibition of excitatory effects of dopamine injected into the limbic system of the rat.

Dopamine (DA) injected unilaterally into the corpus striatum of the brain of the rat after pretreatment with a monoamine oxidase inhibitor, induced contralateral deviation of the head (ED50 = 23 micrograms). Dopamine, administered similarly into the nucleus accumbens septi, induced strong locomotor arousal effects (ED50 = 32 micrograms), as reported by others. Systemic administration of the S(+) isomers of apomorphine (APO) and its N-n-propyl analog (NPA) had no significant action on the effects on posture of DA given intrastriatally, even in large doses. In striking contrast, both agents selectively inhibited the locomotor-arousal effects of DA injected into the accumbens, but (+)NPA was seven times more potent (ED50 = 0.5 mg/kg vs 16 micrograms of DA) and its effects lasted for about 70 min. The dose-effect curves for (+)NPA against two doses of DA demonstrated parallel, lateral displacement, indicating a competitive interaction. These results support the impression that enantiomers and analogs of apomorphine, and especially S(+)N-propylnorapomorphine, have potent antidopaminergic actions that may be selective for limbic areas of the forebrain.