Escitalopram acts by increasing intrasynaptic levels of the neurotransmitter serotonin by blocking the re-uptake of the neurotransmitter into the neuron. Of the SSRIs currently on the market escitalopram has the highest affinity for the human serotonin transporter (SERT). Remarkably, another enantiomer of citalopram (R-citalopram) counteracts to a certain degree the serotonin enhancing action of escitalopram. As a result, escitalopram is a more potent antidepressant than citalopram, which is a mixture of escitalopram and R-citalopram. In order to explain this phenomenon, Sanchez proposed that escitalopram enhances its own binding via an additional interaction with another allosteric site on the transporter.[9] Further research by the same group showed that R-citalopram also enhances binding of escitalopram,[10] and therefore the allosteric interaction cannot explain the observed counteracting effect. However, in the most recent paper the same authors again reversed their findings and reported that R-citalopram decreases binding of escitalopram to the transporter.[11] Although allosteric binding of escitalopram to the serotonin transporter is of unquestionable research interest, its clinical relevance is unclear since binding of escitalopram to the allosteric site is at least 1000 times weaker than to the primary binding site.
In vitro studies using human liver microsomes indicated that CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of escitalopram.
