SNaRIs, NaSSAs, and NaRIs: new agents
for the treatment of depression
by
Kent JM New York State Psychiatric Institute,
Unit 41, New York, NY 10032, USA.
JMK14@columbia.edu
Lancet 2000 Mar 11; 355(9207):911-8

ABSTRACT

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.

TCAs
SSRIs
NARIs
RIMAs
Options
SSRIs/SNRIs
21st century
Sigma ligands
Plato v Aristotle
When SSRIs fail
Antidepressants
Chronic depression
New antidepressants
Future pharmacotherapies
The monoamine hypothesis
Neuropharmacology of serotonin
Selective serotonin reuptake inhibitors (SSRIs): binding profiles

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