Effect of monoamine oxidase A and B and of catechol-O-methyltransferase inhibition on L-DOPA-induced circling behavior.
The effect of enzyme-inhibiting adjuvants on L-DOPA + benserazide-induced contralateral turning in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats was studied. Both the number of turns and the duration of turning were examined. Inhibition of MAO-A with 10 mg/kg Ro 41-1049 increased both parameters; inhibition of COMT with 30 mg/kg Ro 40-7592 had a similar effect. In contrast, inhibition of MAO-B with 10 mg/kg Ro 19-6327 did not change turning behavior. A further potentiation of turning behavior was observed after the combined administration of both the MAO-A and COMT inhibitor. MAO-A inhibition in conjunction with MAO-B inhibition prolonged the duration of L-DOPA-induced turning but had no effect on the number of turns. However, in conjunction with COMT inhibition, 10 mg/kg of the MAO-B inhibitor, Ro 19-6327, significantly affected both the number and duration of turning behavior. An even further potentiation of turning behavior was observed after the combined administration of all three enzyme-inhibitors.
Heeringa
M J
MJ
Pharmaceutical Research Department, F. Hoffmann-La Roche & Co. Ltd., Basel, Switzerland.
d'Agostini
F
F
DeBoer
P
P
DaPrada
M
M
Damsma
G
G
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001577:Benzophenones / Q000494:pharmacology; D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009596:Nitrophenols; D016627:Oxidopamine; D010848:Picolinic Acids / Q000494:pharmacology; D051381:Rats; D012399:Rotation; D013844:Thiazoles / Q000494:pharmacology; D000077867:Tolcapone
D000978:Antiparkinson Agents; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D009596:Nitrophenols; D010848:Picolinic Acids; D013844:Thiazoles; C063456:Ro 41-1049; C059303:lazabemide; D007980:Levodopa; D016627:Oxidopamine; D000077867:Tolcapone