Abstract
The clinically important antidepressant fluoxetine is established as a selective serotonin reuptake inhibitor. This study demonstrates that fluoxetine also interacts with the GABAA receptor complex. At concentrations above 10 μM fluoxetine inhibited the binding of both [3H]GABA (IC50 = 2 mM) and [3H]flunitrazepam (IC50 = 132 μM ) to the GABAA receptor complex in brain cortical membranes. Low fluoxetine concentrations (1 nM) enhanced GABA-stimulated Cl− uptake by a rat cerebral cortical vesicular preparation. At higher concentrations (100 μM and 1 mM), however, fluoxetine inhibited GABA-stimulated Cl− uptake, an effect related to a reduction in Emax. These observations might assist in an explanation of the basis of the antidepressant action of fluoxetine.
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Tunnicliff, G., Schindler, N.L., Crites, G.J. et al. The GABAA Receptor Complex as a Target for Fluoxetine Action. Neurochem Res 24, 1271–1276 (1999). https://doi.org/10.1023/A:1020977123968
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DOI: https://doi.org/10.1023/A:1020977123968