title: S(+)Apomorphines. Selective inhibition of excitatory effects of dopamine injected into the limbic system of the rat.
abstract: 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.
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects; D018492:Dopamine Antagonists; D008032:Limbic System / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects; D011187:Posture; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*
chemical_list: D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; C009074:N-n-propylnorapomorphine; D001058:Apomorphine