Structure and mechanism of action

The chemical structures of duloxetine' venlafaxine' and milnacipran are individually distinct. These drugs selectively inhibit the reuptake of serotonin and norepinephrine and are referred to as serotonin-nor-epinephrine reuptake inhibitors (SNRI). Similar to tricyclics, the analgesic effects of SNRIs are most likely mediated by increases in serotonin and norepinephrine levels' which in turn facilitate activation of the descending inhibitory pathways. Venlafaxine has greater affinity for the serotonin transporter' but noradrenergic reuptake activity increases in a dose-dependent fashion.84

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