Neuroprotective effects of the MAO-B inhibitor, PF9601N, in an in vivo model of excitotoxicity.

Abstract

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.

• Authors: Irene Bolea, Maria Alessandra Colivicchi, Chiara Ballini, José Marco-Contelles, Keith Francis Tipton, Mercedes Unzeta, Laura Della Corte
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 20 Issue 7 Pg. 641-50 (Jul 2014) ISSN: 1755-5949 [Electronic] England
• PMID: 24767579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Excitatory Amino Acid Agonists
• Indoles
• Monoamine Oxidase Inhibitors
• N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine
• Neuroprotective Agents
• 3,4-Dihydroxyphenylacetic Acid
• Monoamine Oxidase
• Dopamine

Topics

• 3,4-Dihydroxyphenylacetic Acid (metabolism)
• Animals
• Corpus Striatum (drug effects, enzymology)
• Dopamine (metabolism)
• Excitatory Amino Acid Agonists (toxicity)
• Indoles (pharmacology)
• Male
• Microdialysis (methods)
• Monoamine Oxidase (metabolism)
• Monoamine Oxidase Inhibitors (pharmacology)
• Neuroprotective Agents (pharmacology)
• Random Allocation
• Rats
• Rats, Wistar