Editing Serotonin (section)

====Termination====
Serotonergic action is terminated primarily via [[reuptake|uptake]] of 5-HT from the synapse. This is accomplished through the specific [[monoamine transporter]] for 5-HT, [[Serotonin transporter|SERT]], on the presynaptic neuron. Various agents can inhibit 5-HT reuptake, including [[cocaine]], [[dextromethorphan]] (an [[antitussive]]), [[tricyclic antidepressants]] and [[selective serotonin reuptake inhibitor]]s (SSRIs). A 2006 study found that a significant portion of 5-HT's synaptic clearance is due to the selective activity of the [[plasma membrane monoamine transporter]] (PMAT) which actively transports the molecule across the membrane and back into the presynaptic cell.<ref name="pmid 1828907">{{cite journal | vauthors = Zhou M, Engel K, Wang J | title = Evidence for significant contribution of a newly identified monoamine transporter (PMAT) to serotonin uptake in the human brain | journal = Biochemical Pharmacology | volume = 73 | issue = 1 | pages = 147–154 | date = January 2007 | pmid = 17046718 | pmc = 1828907 | doi = 10.1016/j.bcp.2006.09.008 }}</ref>

In contrast to the high affinity of SERT, the PMAT has been identified as a low-affinity transporter, with an apparent ''K''<sub>m</sub> of 114 micromoles/l for serotonin, which is approximately 230 times higher than that of SERT. However, the PMAT, despite its relatively low serotonergic affinity, has a considerably higher transport "capacity" than SERT, "resulting in roughly comparable uptake efficiencies to SERT ... in heterologous expression systems."<ref name="pmid 1828907" /> The study also suggests that the administration of SSRIs such as [[fluoxetine]] and [[sertraline]] may be associated with an inhibitory effect on PMAT activity when used at higher than normal dosages ([[IC50|IC<sub>50</sub>]] test values used in trials were 3–4 fold higher than typical prescriptive dosage).