Effect of monoamine oxidase A and B and of catechol-O-methyltransferase inhibition on L-DOPA-induced circling behavior

被引:0
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作者
M. J. Heeringa
F. d'Agostini
P. DeBoer
M. DaPrada
G. Damsma
机构
[1] F. Hoffmann-La Roche & Co. Ltd,Pharmaceutical Research Department
[2] University Center for Pharmacy,Department of Medicinal Chemistry
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Monoamine oxidase; catechol-O-methyltransferase; Ro 41–1049; Ro 19–6327; Ro 40–7592; Parkinson's disease; 6-hydroxydopamine; behavior;
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摘要
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 10mg/kg Ro 41–1049 increased both parameters; inhibition of COMT with 10mg/kg Ro 40–7592 had a similar effect. In contrast, inhibition of MAO-B with 10mg/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, 10mg/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.
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页码:593 / 603
页数:10
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