Stereospecific reduction of haloperidol in human tissues.

In the current study, we have examined the catalytic activity and stereospecificity of haloperidol (HP) reductase activity in the cytosolic fractions of human brain and liver and in whole blood. The reductase activity was NADPH-dependent and inhibited by menadione, features typical of the ketone reductases (EC 1.2.1). The Vmax in the brain was about 4-fold higher than in the liver. Moreover, the reaction was stereospecific in that only the S(-) enantiomer was detected in brain and blood and 99.2 +/- 0.1% of the reduced HP (RHP) produced in the liver was S(-). The potential clinical implications of our results are unknown because until now all binding and pharmacodynamic studies with RHP have been performed with the racemate.