Dopamine transporter and Norepinephrine transporter (DAT and NET)

The dopamine transporter (DAT) and norepinephrine transporter (NET) are closely related members of the solute carrier SLC6 family, responsible for the reuptake of their respective monoamine neurotransmitters—dopamine and norepinephrine—from the synaptic cleft back into presynaptic neurons[2][5][7][9]. Both are integral membrane proteins characterized by 12 transmembrane domains and are structurally and functionally homologous, with substantial overlap in substrate and inhibitor specificity. DAT is encoded by the SLC6A3 gene and primarily clears dopamine, especially in the striatum, whereas NET (encoded by SLC6A2) primarily clears norepinephrine but, particularly in regions like the prefrontal cortex, can also play a significant role in dopamine reuptake[5][8][9]. Inhibition of either transporter increases synaptic concentrations of the relevant neurotransmitter, which underlies the therapeutic actions of various antidepressants, psychostimulants, and other neuropsychiatric drugs[2][4][6]. These transporters are validated drug targets for multiple CNS conditions, but modulation carries risks, especially regarding abuse liability and cardiovascular effects[4][6]. Both proteins are the focus of extensive research into neurological and psychiatric diseases and are actively targeted in drug discovery[2][6].

Other names

Dopamine active transporter (DAT)SLC6A3Noradrenaline transporter (NET)SLC6A2neuronal monoamine transporter

Inhibition of dopamine and/or norepinephrine reuptake by blocking DAT and/or NET, increasing extracellular neurotransmitter levels In some cases, also act as releasing agents (e.g., amphetamines induce release in addition to blocking reuptake)