In a recent publication in Science, a team of researchers showed a possible mechanism of action for Fluoxetine. According to these scientists, it works through a completely new inhibitory pathway, which can also explain the lengthy and for patients often very frustrating waiting time before SSRIs work clinically. They found that in mice chronically fed with Fluoxetine, the expression of the gene that encodes the blueprint of SERT is reduced, which means less SERT is available to remove serotonin from the synapse. This is a surprising finding in itself, still, the mechanism how Fluoxetine down-regulates the SERT expression is even more surprising.
How Prozac works
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