Reduced haloperidol: effects on striatal dopamine metabolism and conversion to haloperidol in the rat.

Acute injection of rats with either haloperidol or reduced haloperidol (1 mg/kg, IP) greatly increased the striatal concentrations of the acidic dopamine metabolites, indicating enhanced turnover of dopamine. The effect of reduced haloperidol was almost as great as that of haloperidol. Reduced haloperidol, however, was much less efficient (about 400 times) than haloperidol in displacing [3H]spiperone binding to striatal membranes in vitro. In agreement with the above results, reduced haloperidol was found to be oxidized to haloperidol, so that 2 h after injection of reduced haloperidol the concentrations of haloperidol and reduced haloperidol were equal in the striatum. The apparent conversion of reduced haloperidol to haloperidol was much quicker in liver than in plasma or brain, and it is suggested that the conversion primarily occurs in the liver. Before drawing any definite conclusion about the possible central activity of reduced haloperidol, further studies with other animal species are needed.