Monoamine oxidase A inhibition by fluoxetine: an in vitro and in vivo study.
Monoamine oxidase A (MAO-A) inhibition was investigated both in vitro and in vivo in rat brains by using the radioligand, 18F-fluoroclorgyline (N-[3-(2',4'-dichlorophenoxy)-2-18F-fluoropropyl]-N-methylpropa rgylamine). 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 microM 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 18F-fluoroclorgyline and binding affinity, -log IC50 (R2 = 0.979). An acute dose of 20 mg/kg of fluoxetine inhibited binding of 18F-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.
Mukherjee
J
J
Franklin McLean Institute, Department of Radiology, The University of Chicago, Illinois 60637, USA. jogeshwar_mukherjee@ketthealth.com
Yang
Z Y
ZY
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D003010:Clorgyline / Q000031:analogs & derivatives / Q000378:metabolism; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D008024:Ligands; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018687:Antidepressive Agents, Second-Generation; D008024:Ligands; D008996:Monoamine Oxidase Inhibitors; D005473:Fluoxetine; C085565:fluoroclorgyline; D008995:Monoamine Oxidase; C036139:norfluoxetine; D003010:Clorgyline