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- The effects of harman and norharman on dopamine content and L-DOPA-induced cytotoxicity wereinvestigated in PC12 cells. Harman and norharman decreased the intracellular dopamine content for 24 h. TheIC 50 values of harman and norharman were 20.4 µM and 95.8 µM, respectively. Tyrosine hydroxylase (TH)activity and TH mRNA levels were also decreased by 20 µM harman and 100 µM norharman. Under the sameconditions, the intracellular cyclic AMP levels were decreased by harman and norharman. In addition, harmanand norharman at concentrations higher than 80 µM and 150 µM caused cytotoxicity at 24 h in PC12 cells.Non-cytotoxic ranges of 10-30 µM harman and 50-150 µM norharman inhibited L-DOPA (20-50 µM)-inducedincreases of dopamine content at 24 h. Harman at 20-150 µM and norharman at 100-300 µM also enhanced L-DOPA (20-100 µM)-induced cytotoxicity at 24 h. These results suggest that harman and norharman decreasedopamine content by reducing TH activity and aggravate L-DOPA-induced cytotoxicity in PC12 cells.

The Harman and Norharman Reduced Dopamine Content and Induced Cytotoxicity in PC12 Cells