SNaRIs, NaSSAs, and NaRIs: new agents for the treatment of depression

A major goal of antidepressant development is to improve on preceding drug classes with agents with greater specificity (and therefore fewer unwanted side-effects) and with more rapid onset of antidepressant action. To this end, four antidepressants with significantly distinct pharmacological characteristics have been recently introduced: venlafaxine, nefazodone, mirtazapine, and reboxetine. Venlafaxine is the first antidepressant in a new drug class referred to as the serotonin noradrenergic reuptake inhibitors (SNaRIs). Nefazodone is a weaker serotonin and norepinephrine reuptake inhibitor, but a potent serotonin 5-HT2 receptor antagonist. Mirtazapine is a potent antagonist of central 2alpha-adrenergic autoreceptors, and heteroreceptors and is an antagonist of serotonin 5-HT2 and 5-HT3 receptors. The result of these actions is to increase both noradrenergic and specific (5-HT1) serotonergic transmission, and mirtazapine has therefore been termed a noradrenergic and specific serotonergic antidepressant (NaSSA). Reboxetine is the first selective noradrenaline reuptake inhibitor (NaRI) to be introduced since the tricyclics, and lacks immediate serotonergic effects.