Norepinephrine Involvement in Antidepressant Action

Because of the introduction and popularity of the selective serotonin reuptake inhibitor (SSRI) antidepressants,much attention was centered on the indolealkylamine 5-hydroxytryptamine, or serotonin. Tosome extent, this focus on serotonin occurred at the expense of the catecholamine neurotransmitter norepinephrine.Nevertheless, it has been apparent for almost 40 years that selective blockers of norepinephrinereuptake may be antidepressants (e.g., desipramine). This brief review covers the acute pharmacologiceffects that may be responsible for the efficacy of currently marketed antidepressants as well as thatof reboxetine, a newly developed selective norepinephrine reuptake inhibitor. Also discussed is the factthat the acute pharmacologic profile of selective reuptake inhibitors often predicts effects they producewhen given long term. For example, the long-term administration of SSRIs produces certain effects onserotonergic systems, but not noradrenergic ones. By contrast, selective norepinephrine reuptake inhibitors,when given long term, modify certain noradrenergic parameters, but not serotonergic indices. Finally,it is speculated how drugs that enhance central noradrenergic transmission might ameliorate thesymptoms of depression.