| Abstract | dc.description.abstract | (S)-(1)-boldine, an aporphine alkaloid displaying antioxidative and dopaminergic properties, and six of its derivatives (glaucine,
3-bromoboldine, 3-iodoboldine, 8-aminoboldine, 8-nitrosoboldine and 2,9-O,O9 -dipivaloylboldine) were tested for these properties in
comparison with their parent compound. All the tested compounds displayed in vitro antioxidative properties equal to or slightly weaker
than those of boldine, and equal to or stronger than (6)-6-hydroxy-2,5,7,8,-tetramethylchromane-2-carboxylic acid (Trolox), a
3 water-soluble vitamin E analogue, used as a reference compound. All the aporphine compounds tested displaced [ H]SCH 23390 and
3 [ H]raclopride from their specific binding sites in rat striatum. When tested on dopamine (DA) metabolism in the striatum of B6CBA
mice, all the compounds, except 8-aminoboldine, increased striatal levels of DOPAC and HVA, and the HVA/DA ratio, indicating that
they cross the blood–brain barrier and that they seem to act as dopamine antagonists in vivo. B6CBA mice were sensitive to the
neurotoxic action of MPTP on dopaminergic neurons as indicated by the strongly decreased striatal levels of DA, DOPAC and HVA
following administration of MPTP (20 mg/ kg, i.p.). Among these aporphine derivatives, only 3-bromoboldine was able to reduce the
MPTP-induced decrease of striatal levels of DA and DOPAC, whereas (R)-apomorphine (5 mg/ kg, s.c.) and acetylsalicylic acid (100
mg/ kg, i.p.), used as reference compounds, were very active. These data suggest that potent in vitro antioxidative properties and the
ability to cross the blood–brain barrier are not sufficient criteria to predict the inhibition of neuronal degeneration induced by MPTP. | es_CL |
