The inhibitory effects of liriodenine, an aporphine isoquinoline alkaloid, on dopamine biosynthesis and L-DOPA-induced dopamine content increases in PC12 cells were investigated. Treatment of PC12 cells with 5-10 ${mu}M$ liriodenine significantly decreased the intracellular dopamine content in a concentration-dependent manner ($IC_{50}$ value, 8.4 ${mu}M$). Liriodenine was not cytotoxic toward PC12 cells at concentrations up to 20 ${mu}M$. Tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) activities were inhibited by 10 ${mu}M$ liriodenine to 20-70% and 10-14% of control levels at 3-12 h, respectively; TH activity was more influenced than AADC activity. The levels of TH mRNA, intracellular cyclic AMP and basal $Ca^{2+}$ concentration were also decreased by 10 ${mu}M$ liriodenine. In addition, 10 ${mu}M$ liriodenine reduced L-DOPA (20-100 ${mu}M$)-induced increases in dopamine content. However, 10 ${mu}M$ liriodenine resulted in a protective effect against L-DOPA (50-100 ${mu}M$)-induced cytotoxicity. These results suggest that liriodenine regulates dopamine biosynthesis by partially reducing TH activity and TH gene expression and has protective effects against L-DOPA-induced cytotoxicity in PC12 cells.