Potentiation of central effects of L-dopa by an inhibitor of catechol-O-methyltransferase.
The effects of a COMT-inhibitor, U-0521, and a MAO-B-inhibitor, 1-deprenyl, on L-dopa-induced circling behaviour were compared in 6-OHDA-lesioned rats. The actions of U-0521 and 1-deprenyl on the anti-cataleptic effect of L-dopa were also studied. Both U-0521 and 1-deprenyl were found to potentiate L-dopa-induced circling behaviour and anti-cataleptic effect of L-dopa. In both test systems the L-dopa potentiation of 1-deprenyl was longer-lasting than that caused by U-0521. Thus inhibition of COMT, like inhibition of MAO, is able to enhance the central effects of L-dopa. This principle might be beneficial in the treatment of Parkinson's disease especially if COMT-inhibitors with greater performance can be developed.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology; D065098:Catechol O-Methyltransferase Inhibitors; D002490:Central Nervous System / Q000187:drug effects*; D006220:Haloperidol / Q000009:adverse effects; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology*; D011427:Propiophenones / Q000494:pharmacology*; D051381:Rats; D012642:Selegiline / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms
D065098:Catechol O-Methyltransferase Inhibitors; D010627:Phenethylamines; D011427:Propiophenones; D012642:Selegiline; D007980:Levodopa; C006104:U 0521; D006220:Haloperidol