Serotonin/norepinephrine transporter

Class

SNRI

The serotonin transporter (SERT) and norepinephrine transporter (NET) are membrane proteins that recapture the neurotransmitters serotonin and norepinephrine from the synaptic cleft after they have been released, ending their signal and recycling them into the presynaptic neuron. Serotonin-norepinephrine reuptake inhibitors (SNRIs) block both transporters, so more of each neurotransmitter remains available in the synapse to continue signaling at postsynaptic receptors. Serotonin circuits are implicated in mood, anxiety, and pain modulation, while norepinephrine circuits contribute to alertness, arousal, and descending inhibition of pain signals in the spinal cord. Combining inhibition of both transporters, rather than targeting either alone, is intended to produce broader effects on mood and on pain perception than a selective serotonin reuptake inhibitor typically achieves, since norepinephrine pathways add an independent route of symptom modulation. This dual mechanism is used broadly in depressive and anxiety disorders and in certain chronic pain conditions, including neuropathic pain and diffuse musculoskeletal pain syndromes, where descending noradrenergic pain-inhibitory pathways are thought to be relevant. The rationale for dual transporter blockade rests on the complementary, only partially overlapping roles that serotonin and norepinephrine play in mood regulation and pain processing.