Effect of 3',4'-dihydroxy-2-methyl-propriophenone (U-0521) on catechol-O-methyltransferase activity and on DOPA accumulation in rat red blood cells and corpus striatum.
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.
D000818:Animals; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D003342:Corpus Striatum / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism*; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D008297:Male; D011427:Propiophenones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D065098:Catechol O-Methyltransferase Inhibitors; D011427:Propiophenones; D007980:Levodopa; C006104:U 0521; D002394:Catechol O-Methyltransferase