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Serotonin norepinephrine reuptake inhibitors (SNRIs) work by inhibiting the reuptake of the neurotransmitters serotonin and norepinephrine. This results in an increase in the extracellular concentrations of serotonin and norepinephrine and therefore an increase in neurotransmission. The three SNRIs milnacipran, duloxetine, and venlafaxine have different affinity and selectivity profiles. Milnacipran and duloxetine inhibit the reuptake of serotonin and norepinephrine at all doses. In contrast, venlafaxine selectively inhibits the reuptake of serotonin at low doses, but this serotonin transporter specificity disappears as the dose increases (i.e., it acts as an SNRI). In addition, the SNRIs, as well as the SSRIs, have few significant side effects because they interact only infrequently with other neurotransmitter receptors. Milnacipran and duloxetine seem to have fewer side effects and essentially show no cardiovascular toxicity. However, venlafaxine appears the least well-tolerated because of a high incidence of serotonergic adverse events (nausea, sexual dysfunction, withdrawal problems) and dose-dependent hypertension. SNRIs have increased efficacy and good tolerability and are used for the treatment of anxiety disorders and chronic pain. Our results suggest that SNRIs may have more advantages than other kinds of antidepressants and that the differences in the pharmacological profiles of each should be understood when using them.

Comparison of pharmacological profiles of serotonin norepinephrine reuptake inhibitors