Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

Serotonin-norepinephrine reuptake inhibitors (SNRIs) prevent presynaptic reuptake of serotonin and norepinephrine in the synaptic cleft.  SNRIs are used to treat depression and anxiety, as well as pain disorders.  They have similar safety profiles to selective serotonin reuptake inhibitors (SSRIs), but many SNRIs can be associated with elevations in blood pressure.

In the brainstem, serotonergic (serotonin-releasing) neurons are found primarily in the raphe nuclei, located in the midbrain, pons, and medulla.  Noradrenergic (norepinephrine-releasing) neurons are found in the locus coeruleus, located in the dorsal pons.  Axons from these cell bodies project widely throughout the CNS to synapse on structures such as the cerebral cortex, thalamus, hypothalamus, cerebellum, hippocampus, and spinal cord.

Both serotonin and norepinephrine are implicated in neuronal pathways affecting mood and anxiety.  In the synapse, SNRIs inhibit both serotonin and norepinephrine transporter proteins and block the presynaptic reuptake of serotonin and norepinephrine, increasing their availability in the synaptic cleft.  This action strengthens postsynaptic serotonin and norepinephrine receptor activity, leading to downstream therapeutic effects on mood and anxiety.