A Less Selective Inhibitor

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Science  28 Jun 2013:
Vol. 340, Issue 6140, pp. 1500
DOI: 10.1126/science.340.6140.1500-c

The most widely used antidepressant drugs are selective serotonin reuptake inhibitors. They block the high-affinity serotonin transporter and thereby prevent the retrieval of serotonin from the extracellular fluid into nerve terminals. Unfortunately, many individuals suffering from depression experience minimal or no improvement when taking these drugs; new medications would help patients who respond poorly to selective serotonin reuptake inhibitors. The organic cation transporters and the plasma membrane monoamine transporter have low affinity for serotonin but a high transport capacity. Decynium-22 is an inhibitor of this group of transporters and has been shown to block serotonin uptake into brain synaptosomes. Horton et al. report that the antidepressant-like effect of a selective serotonin reuptake inhibitor can be strengthened significantly by coadministration of decynium-22. This group of decynium-22–sensitive transporters may thus be a promising target for the development of new antidepressant drugs. These drugs might act either in combination with existing antidepressants or perhaps all on their own by blocking one or more of the organic cation transporters or the plasma membrane monoamine transporter.

J. Neurosci. 33, 10534 (2013).

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