The noradrenaline (NA), dopamine (DA) and serotonin (5HT) reuptake inhibitory potency of deprenyl, the highly selective and irreversible inhibitor of MAO-B, methamphetamine enantiomers, and some other MAO inhibitors (clorgyline, J-508, J-511, J-512, J-516, LK-63, U-1424, 2-HxMP) was compared. In vitro hypothalamic NA reuptake was inhibited by (+)-, and (-)-methamphetamine, (+)-J-508 and (+)-deprenyl (IC50: 0.35, 3.5, 17.0 and 17.8 μmol/l, respectively), and U-1424, J-512, J-516, LK-63 and 2-Hx-MP showed IC50 >1000 μmol/l. Striatal DA reuptake was inhibited by (+)-, and (-)-methamphetamine, (+)-, and (-)-deprenyl and clorgyline with IC50 of 0.6, 42.0, 24.0, 98.6 and 27.0 μmol/l, respectively, however the other compounds were ineffective. Hippocampal 5HT reuptake was slightly inhibited by clorgyline (IC50 205.0 μmol/l), while the other MAO-inhibitors were devoid of potency. Data suggest that potency and selectivity of MAO inhibition and reuptake inhibition are independent features of the compounds, and metabolism of deprenyl results in increased noradrenaline and dopamine reuptake inhibition.
|Number of pages||8|
|Publication status||Published - Dec 1 2000|
- Biogenic amines
- MAO inhibitors
ASJC Scopus subject areas