Evaluation of monoamine oxidase B inhibition by fluoxetine (Prozac): an in vitro and in vivo study.
Inhibition of monoamine oxidase B was investigated both in vitro and in vivo in rats by using the radioligand, N-(6-[18F]fluorohexyl)-N-methylpropargylamine ([18F]FHMP). Binding affinities of five compounds, deprenyl, clorgyline, fluoxetine, norfluoxetine and citalopram were studied. Fluoxetine and norfluoxetine showed affinities of 17 and 13 microM for monoamine oxidase B, respectively. Acute doses of fluoxetine and norfluoxetine (20 mg/kg) also significantly inhibited (10 to 15%) the binding of the radioligand in vivo while citalopram showed lower affinity (140 microM) for monoamine oxidase B and little effect in vivo. The in vivo effects of the various drugs were directly comparable to their in vitro affinities for binding to monoamine oxidase B in the correlation plot of percent control in vivo binding of [18F]FHMP and binding affinity, -logIC50 (R2 = 0.989). These results provide evidence for a potential role of monoamine oxidase B inhibition in the therapeutic effects of Prozac.
Mukherjee
J
J
Department of Radiology, Franklin McLean Institute, The University of Chicago, IL 60637, USA. j-mukherjee@uchicago.edu
Yang
Z Y
ZY
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley
D018687:Antidepressive Agents, Second-Generation; D008996:Monoamine Oxidase Inhibitors; D005473:Fluoxetine; D008995:Monoamine Oxidase