Mechanism of Reuptake Inhibition
The main objective of a reuptake inhibitor is to substantially decrease the rate by which neurotransmitters are reabsorbed into the presynaptic neuron, increasing the concentration of neurotransmitter in the synapse. This increases neurotransmitter binding to pre- and postsynaptic neurotransmitter receptors. Depending on the neuronal system in question, a reuptake inhibitor can have drastic effects on cognition and behavior. Non-competitive inhibition of the bacterial homologue LeuT by tricyclic antidepressants resulted from binding of these inhibitors in the extracellular permeation pathway. However, the competitive nature of serotonin transport inhibition by antidepressants suggests that in neurotransmitter transporters, they bind in a site overlapping the substrate site.
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