NRIs reuptake inhibitors

Listing of antidepressants grouped by principal mechanism of action in the synapse. Abbreviations MAOI—irreversible = irreversible monoamine oxidase inhibitor MAOI—reversible = reversible monoamine oxidase inhibitor NDRl = norepinephrine/ dopamine reuptake inhibitor NRI = norepinephrine reuptake inhibitor NSRl = norepinephrine/serotonin reuptake inhibitor NSSA = norepinephrine/specific serotonin agonist SRI = serotonin reuptake inhibitor SRl/serotonin-2 blocker = serotonin reuptake inhibitor and serotonin-2 receptor antagonist. 

Reboxetine was first introduced to the European market in 1997 for the treatment of depression it is not yet available in the United States. Reboxetine represents a novel antidepressant class, the selective noradrenaline reuptake inhibitors (NRIs). 

FIGURE 6—46. Icon of a selective norepinephrine reuptake inhibitor (NRI). 

FIGURE 6—47. In this diagram, the norepinephrine reuptake inhibitor (NRI) portion of the selective NRI molecule is shown inserted in the norepinephrine reuptake pump, blocking it and causing an antidepressant effect. 

FIGURE 6-48. Shown here is the icon of a norepinephrine and dopamine reuptake inhibitor (NDRI). In this case, four of the five pharmacological properties of the tricyclic antidepressants (TCAs) (Fig. 6—27) were removed. Only the norepinephrine reuptake inhibitor (NRI) portion remains to this is added a dopamine reuptake inhibitor action (ORI). 

FIGURE 7—40. Adrenergic combo 1 Bupropion plus norepinephrine reuptake inhibitor (NRI). Here the NE actions of bupropion are double-boosted by the NRI (either selective reboxetine or nonselective desipramine, maprotilene, nortriptyline, or protriptyline). Dopamine is single-boosted by bupropion only. 

FIGURE 6-27. Shown here is an icon of a tricyclic antidepressant (TCA). These drugs are actually five drugs in one (1) a serotonin reuptake inhibitor (SRI) (2) a norepinephrine reuptake inhibitor (NRI) (3) an anticholinergic/antimuscarinic drug (Ml) (4) an alpha adrenergic antagonist (alpha) and (5) an antihistamine (HI). 

FIGURE 6—29- Therapeutic actions of the tricyclic antidepressants—part 2. In this diagram, the icon of the TCA is shown with its norepinephrine reuptake inhibitor (NRI) portion inserted into the norepinephrine reuptake pump, blocking it and causing an antidepressant effect. Thus, both the serotonin reuptake portion (see Fig. 6—28) and the NRI portion of the TCA act pharmacologically to cause an antidepressant effect. 

NE molecules released into the synaptic space are reabsorbed back into the presynaptic neuron by the membrane NE transporter (NET). This process requires ATP. The NET is a target for numerous drugs. Several tricyclic antidepressants (TCA), such as imipramine, non-specifically inhibit both NET and 5-HT (5-HTT) transporters (Corrodi and Fuxe 1968). Other TCAs, called norepinephrine reuptake inhibitors (NRIs), such as desipramine, specifically inhibit the NET (Curet et al., 1992 Lacroix et al., 1991). There are also non-tricyclic selective inhibitors of the NET, called selective norepinephrine reuptake inhibitors (SNeRIs), and dual inhibitors of the NET and 5-HTT (SNRIs). The examples for SneRIs and SNRIs are reboxetine and venlafaxine, respectively (Beique et al., 1998a Beique et al., 1998b Beique et al., 1999 Dawson et al., 1999 Szabo and Blier 2001c). 

Reboxetine Morpholine Selective noradrenaline reuptake inhibitor (NRI or NARI)... 

Synthesis and activity of 1-(3-amino-2-hydroxy-1-phenyipropyi)indoiin-2-ones Discovery of seiective norepinephrine reuptake inhibitor WAY-315193 (NRi-193)... 

Norepinephrine (NE) and serotonin (5-HT) are key neurotransmitters involved with the pathophysiology of depression. Norepinephrine reuptake inhibitors (NRIs) increase extracellular... 

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