Monoamine oxidase a inhibition by fluoxetine: An in vitro and in vivo study

✍ Scribed by Jogeshwar Mukherjee; Zhi-Ying Yang

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 77 KB
• Volume: 31
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(19990315)31:4<285::aid-syn6>3.0.co;2-5

✦ Synopsis

Monoamine oxidase A (MAO-A) inhibition was investigated both in vitro and in vivo in rat brains by using the radioligand, 18 F-fluoroclorgyline (N-[3-(2Ј,4Јdichlorophenoxy)-2-18 F-fluoropropyl]-N-methylpropargylamine). In vitro binding affinities of six compounds, clorgyline, Ro 41-1049, deprenyl, fluoxetine, norfluoxetine and citalopram, were studied. Fluoxetine and norfluoxetine showed in vitro affinities of 36.5 and 68 µM for MAO-A, respectively. Fluoxetine and norfluoxetine also significantly inhibited (more than 20%) the binding of the radioligand in vivo while citalopram and deprenyl showed very poor affinities in vitro for MAO-A and had no effect in vivo. The in vivo effects of the various drugs were directly comparable to their in vitro affinities for binding to MAO-A as seen in the correlation plot of percent control in vivo binding of 18 F-fluoroclorgyline and binding affinity, -log IC 50 (R 2 ϭ 0.979). An acute dose of 20 mg/kg of fluoxetine inhibited binding of 18 F-fluoroclorgyline by more than 20%, while lower doses had some significant effects. These results provide evidence on the in vitro and in vivo inhibition of monoamine oxidase A by fluoxetine.