The molecular mechanism of amphetamine action (358.2)

Serotonin plays an important role as neurotransmitter in the brain in a number of circuits which can also be linked to reward and cognition. The transporters for these neurotransmitters are located in presynaptic specializations; they inactivate serotonin‐mediated neurotransmisison following exocytotic release by a simple reuptake mechanism. Recent crystallographic examination of bacterial homologs to the mammalian neurotransmitter transporters provides a structural scaffold which supports transport by an alternative access mechanism. Serotonin transporters are the clinically relevant target of antidepressant drugs; they inhibit the reuptake of monoamines by competitively blocking the transporters. Thereby, these compounds enhance the extracellular concentration of serotonin which is relevant for clinical success. Serotonin transporters also provide a route for non‐exocytotic neurotransmitter release (efflux) triggered by amphetamines. Recent advancement in the understanding of the structural and molecular mechanisms of amphetamine‐induced efflux via serotonin transporters will be discussed. Furthermore, the mechanisms underlying the activity of the recently introduced “bath salts”, a class of amphetamine‐like compounds, will be highlighted.