کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6264232 | 1613969 | 2012 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Research ReportModulations of brain amines and dopaminergic behavior by a novel, reversible and selective MAO-B inhibitor Research ReportModulations of brain amines and dopaminergic behavior by a novel, reversible and selective MAO-B inhibitor](/preview/png/6264232.png)
Monoamine oxidase (MAO) B is a validated target for many neurodegenerative diseases. Recently we have reported a few pyrazolines as reversible and selective MAO-B inhibitors. Amongst them, we have selected the most potent analog, NP-9 (Ki=0.31Â nM; selectivity index, MAO-B/A more than 100) for the current preclinical study. It selectively inhibited MAO-B activity in liver and brain. Maximum inhibition was observed at 7Â mg/kg, i.p., dose, which was reversed after 8Â h. We did not observe any alteration in amines level on its acute administration, whereas, on its chronic administration we observed significant increase in striatal dopamine level. Other noteworthy observations were (a) it markedly potentiated the 2-phenylethylamine induced stereotype behavior, (b) it partially reversed the reserpine induced oral dyskinesia, (c) it protected the reserpine induced glutathione oxidation (in cerebrum) and (d) no hypertensive crisis was observed on tyramine co-treatment. The study provides a preclinical basis to NP-9 for MAO-B inhibition.
⺠NP-9 a pyrazoline derivative, identified (in vitro) as reversible MAO-B inhibitor. ⺠In this study it reversibly and selectively inhibited cerebral MAO-B activity. ⺠It could not alter brain amines level on acute administration. ⺠It specifically increased striatal DA level on chronic administration. ⺠It modulated behaviors, induced by PEA (stereotype) and reserpine (oral dyskinesia).
Journal: Brain Research - Volume 1470, 27 August 2012, Pages 45-51