Serotonin‐norepinephrine reuptake inhibitors and the influence of binding affinity (Ki) on analgesia

Summary What is known and objective Serotonin‐norepinephrine reuptake inhibitors (SNRIs) are commonly used for various psychiatric conditions and neuropathic pain syndromes. SNRIs inhibit the reuptake of serotonin (5‐HT) and norepinephrine (NE); however, NE reuptake inhibition is thought to be the primary mediator for their analgesic effect. Comment Key differences in pharmacodynamics and receptor affinities exist between SNRIs. The selectivity for each monoamine differs among SNRIs based on the agent's affinity and activity at the monoamine reuptake transporter. We review differences in receptor affinities and monoamine selectivity among SNRIs and the corresponding clinical impact. What is new and conclusion The varying selectivity for 5‐HT and NE among the SNRIs may help explain the therapeutic dosing required for neuropathic pain as well as dose‐related adverse effects. It is important to understand the pharmacologic differences among SNRIs, in addition to the data from clinical trials, to guide their safe and effective use.