Biochemical and behavioral effects of boldine and glaucine on dopamine systems

The aporphine alkaloids boldine and glaucine have been reported to show "neuroleptic-like" actions in mice, suggesting that they may act as dopamine antagonists. We have found that in vitro boldine displaces specific striatal [H-3]-SCH 23390 binding with IC50 = 0.4 mu M and [H-3]-raclopride binding with IC50 = 0.5 mu M, while the affinities of glaucine at the same sites are an order of magnitude lower. In vivo, however, 40 mg/kg boldine (IP) did not modify specific striatal [H-3]-raclopride binding and only decreased [H-3]-SCH 23390 binding by 25%. On the other hand, 40 mg/kg glaucine (IP) displaced both radioligands by about 50%. Behaviors (climbing, sniffing, grooming) elicited in mice by apomorphine (0.75 mg/kg SC) were not modified by boldine at doses up to 40 mg/kg (IP) but were almost completely abolished by 40 mg/kg glaucine (IP). In the apomorphine-induced (0.1 mg/kg SC) rat yawning and penile erection model, boldine and glaucine appeared to be similarly effective, inhibiting both behaviors by more than 50% at 40 mg/kg (IP). Boldine and glaucine, injected IP at doses up to 40 mg/kg, were poor modifiers of dopamine metabolism in mouse and rat striatum. These data suggest that boldine does not display effective central dopaminergic antagonist activities in vivo in spite of its good binding affinity at D-1- and D-2-like receptors, and that glaucine, although less effective in vitro, does appear to exhibit some antidopaminergic properties in vivo. (C) 1998 Elsevier Science Inc.