Neuroprotective effects of the MAO-B inhibitor, PF9601N, in an in vivo model of excitotoxicity.
BACKGROUND
PF9601N [N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine] is an inhibitor of monoamine oxidase B (MAO-B), which has shown to possess neuroprotective properties in several in vitro and in vivo models of Parkinson's disease (PD). As there is evidence that excitotoxicity may be implicated in the pathophysiology of several neurodegenerative diseases, the aim of the present work was to investigate the effects of PF9601N in an acute in vivo model of excitotoxicity induced by the local administration of kainic acid during striatal microdialysis in adult rats.


METHODS
The basal and evoked release of neurotransmitters was monitored by HPLC analysis of microdialysate samples and tissue damage was evaluated histologically "ex vivo."


RESULTS
PF9601N (40 mg/kg, single i.p. administration) reduced the kainate-evoked release of glutamate and aspartate and increased taurine release, but it had no effect on the release of dopamine, DOPAC, and HVA. PF9601N pretreatment also resulted in a significant reduction in the kainate-induced astrocytosis, microgliosis, and apoptosis.


CONCLUSIONS
The results suggest PF9601N to be a good candidate for the treatment of neurodegenerative diseases mediated by excitotoxicity.
Departament de Bioquimica i Biologia Molecular, Facultat de Medicina, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Dipartimento di Neuroscienze, Psicologia Area del Farmaco e Salute del Bambino (NEUROFARBA), Università degli Studi di Firenze, Firenze, Italy.
Irene
I
Bolea
Maria Alessandra
MA
Colivicchi
Chiara
C
Ballini
José
J
Marco-Contelles
Keith Francis
KF
Tipton
Mercedes
M
Unzeta
Laura
L
Della Corte
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004298:Dopamine / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis / Q000379:methods; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D018690:Excitatory Amino Acid Agonists; D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; C470996:N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine; D018696:Neuroprotective Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D008995:Monoamine Oxidase; D004298:Dopamine
Amino acids; Dopamine; Glia; Kainate; Microdialysis