Reuptake

Using the commonalities among sequences and hydropathy plot analyses, it was predicted that there are 12 hydrophobic membrane spanning regions in the 'Classical' transporter family.

External and internal "gates" were assigned to pairs of negatively and positively charged residues in the extracellular cavity and near the cytoplasmic ends of TM helices 1 and 8.

Typical neurotransmitter sodium symport (NSS) transporters, which are Na+ and Cl− ion dependent, take advantage of both Na+ and Cl− gradients, inwardly directed across the membrane.

The ions flow down their concentration gradients, in many cases leading to transmembrane charge movement that is enhanced by the membrane potential.

Non-competitive inhibition of the bacterial homologue LeuT by tricyclic antidepressants resulted from binding of these inhibitors in the extracellular permeation pathway.

They presented SERT with varying doses of either citalopram (an SSRI) or desipramine (an inhibitor of norepinephrine reuptake protein, NET).

Horschitz et al. found that after removing citalopram from the system, normal levels of SERT binding site expression returned.

[13] Depression has been suggested to be a result of a decrease of serotonin found in the synapse, although this hypothesis has been challenged since as early as the 1980s[citation needed].

It was initially supported by the successful reduction of depressive symptoms after administration of tricyclic antidepressants (such as desipramine) and SSRIs.

This proposal for the antidepressant mechanism of serotonin reuptake inhibitors does not account for the time course of the therapeutic effect, which takes weeks to months, while transporter inhibition is essentially immediate.

It has been shown that AMPH acts upon trace amine-associated receptor 1 (TAAR1) to induce efflux and reuptake inhibition in the serotonin, norepinephrine, and dopamine transporters.

EAAT2 knockout mice were more prone to lethal and spontaneous seizures and acute brain injuries among the cortex.