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Monoamine oxidase a inhibition by fluoxetine: An in vitro and in vivo study
Author(s) -
Mukherjee Jogeshwar,
Yang ZhiYing
Publication year - 1999
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(19990315)31:4<285::aid-syn6>3.0.co;2-5
Subject(s) - monoamine oxidase , in vivo , monoamine neurotransmitter , fluoxetine , monoamine oxidase a , pharmacology , chemistry , in vitro , monoamine oxidase b , monoamine oxidase inhibitor , serotonin , biology , biochemistry , enzyme , microbiology and biotechnology , receptor
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‐(2′,4′‐dichlorophenoxy)‐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 = 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. Synapse 31:285–289, 1999. © 1999 Wiley‐Liss, Inc.