The novel type B MAO inhibitor PF9601N enhances the duration of L-DOPA-induced contralateral turning in 6-hydroxydopamine lesioned rats.
The present study examined the effect of the highly potent and selective MAO B inhibitor PF9601N on L-DOPA-induced rotational behavior in unilateral nigrostriatal 6-hydroxydopamine lesioned rats. Three doses of PF9601N (20, 40 and 60mg/kg) were administered 30 min before an injection of L-DOPA (25mg/kg), and both contralateral and ipsilateral rotational behavior was measured. In addition, we also studied the effect produced by another MAO B inhibitor, deprenyl (20mg/kg), the MAO A inhibitor, clorgyline (20mg/kg), and the dopamine reuptake inhibitor, GBR2909 (7.5 mg/kg) on L-DOPA-induced rotational behavior. The results showed that PF9601N plus L-DOPA significantly enhanced the duration of contralateral rotational behavior with respect to L-DOPA plus vehicle in a dose-related manner. At the dose of 40 and 60mg/kg, PF9601N produced significantly more overall contralateral turning than L-DOPA plus vehicle, and at the dose of 60mg/kg, PF9601N produced significantly more turning behavior than L-DOPA plus deprenyl. These results suggest that PF9601N may be used as a novel tool in the treatment of Parkinson's disease.
Prat
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Laboratori de Neuropsicofarmacolgia, Institut de Recerca de L'Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. arubioc@hsp.santpau.es
Pérez
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V
Rubi
A
A
Casas
M
M
Unzeta
M
M
D018663:Adrenergic Agents; D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D003342:Corpus Striatum / Q000293:injuries; D015259:Dopamine Agents / Q000009:adverse effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008995:Monoamine Oxidase / Q000187:drug effects*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000188:drug therapy; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology; D013378:Substantia Nigra / Q000293:injuries
D018663:Adrenergic Agents; D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D008996:Monoamine Oxidase Inhibitors; D010879:Piperazines; D012642:Selegiline; D007980:Levodopa; D016627:Oxidopamine; C043425:vanoxerine; D008995:Monoamine Oxidase; D003010:Clorgyline