Sodium-dependent serotonin, noradrenaline, and dopamine transporters (MATs)

The serotonin, norepinephrine, and dopamine transporters (SERT, NET, and DAT) are integral membrane proteins belonging to the solute carrier family 6 (SLC6) that facilitate the reuptake of monoamine neurotransmitters from the synaptic cleft into presynaptic neurons (UniProt P31645, P23975, Q01959). This reuptake mechanism is the primary regulator of the duration and intensity of monoaminergic signaling in the brain, influencing mood, reward, attention, and autonomic functions (PubMed: 24107119). SERT (SLC6A4) is a key target for antidepressants, NET (SLC6A2) is involved in arousal and stress responses, and DAT (SLC6A3) is central to the brain's reward system and motor control (StatPearls: Physiology, Noradrenergic Synapse). Dysregulation of these transporters is linked to major depressive disorder, ADHD, and obesity. Therapeutic agents known as triple reuptake inhibitors (SNDRIs), such as amitifadine and tesofensine, target all three transporters to potentially enhance antidepressant efficacy or induce weight loss, though they carry risks of cardiovascular stimulation and abuse potential due to their effects on dopamine and norepinephrine (PubMed: 23683505).

Other names

Monoamine transportersSERT/NET/DATSLC6A4/SLC6A2/SLC6A3Triple reuptake inhibitor targetsSNDRI targetsSodium-dependent monoamine transporters

Simultaneous inhibition of the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT), preventing the reuptake of serotonin, norepinephrine, and dopamine from the synaptic cleft into the presynaptic neuron, thereby increasing their extracellular concentrations and prolonging their physiological effects (PubMed: 24107119).