The effects of the catechol-O-methyltransferase (COMT) inhibitor 3',4'-dihydroxy-2-methyl-propriophenone (U-0521) were studied in red blood cells (RBC) and corpus striatum in the rat. In vitro U-0521 inhibited RBC COMT activity in a dose-dependent manner with an IC50 of 6 x 10(-6)M. In vivo maximum inhibition (90%) of enzyme activity in RBC was obtained with 250 mg/kg with a peak effect at 5 min and enzyme recovery within 90 min. In U-0521-pretreated rats L-3,4-dihydroxyphenylalanine (L-DOPA) accumulation in RBC and corpus striatum, after injection of L-DOPA, was significantly higher than in nonpretreated rats. The use of COMT inhibitor along with L-DOPA may be of benefit in the treatment of Parkinson's disease.
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