Norepinephrine-selective reuptake inhibitors

Scates, A. C. Doraiswamy, P. M. (2000). Reboxetine a selective norepinephrine reuptake inhibitor for the treatment of depression. Ann. Pharmacother., 34, 1302-12. 

Pharmacology Atomoxetine is a selective norepinephrine reuptake inhibitor. The precise mechanism by which it produces its therapeutic effects in ADHD is unknown, but it is thought to be related to selective inhibition of the presynaptic norepinephrine transporter, as determined in ex vivo uptake and neurotransmitter depletion studies. Pharmacokinetics ... 

Atomoxetine (Strattera) [ADHD/Selective Norepinephrine Reuptake Inhioiter] WARNING Severe liver injury may rarely occur D/C w/ jaundice or TLFT, T frequency of suicidal thoughts Uses ADHD Action Selective norepinephrine reuptake inhibitor Dose Adults Children >70 kg. 40 mg X 3 d, T to 80-100 mg -s- daily-bid Feds <70 kg. 0.5 mg/kg x 3 d, then T 1.2 mg/kg daily or bid (max 1.4 mg/kg or 100 mg) Caution [C, /-] Contra ... 

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

Hajos M, Fleishaker JC, Filipiak-Reisner JK, et al. The selective norepinephrine reuptake inhibitor antidepressant reboxetine pharmacological and clinical profile. CNS Drug Rev. 2004 10 23-44. 

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). 

Reuptake Norepinephrine transporter Tricyclic antidepressants (imipramine, f) Tricyclic norepinephrine reuptake inhibitors (desipiamine, ) Selective norepinephrine reuptake inhibitors (reboxetine, ) Dual serotonin/ norepinephrine reuptake inhibitors (venlafaxine, J.)... 

Selective norepinephrine reuptake inhibitors Desipramine (Norpramin) Nortriptyline (Pamelor, Aventyl) Reboxetine... 

FLUVOXAMINE REBOXETINE May t fluvoxamine levels Reboxetine Is a selective norepinephrine reuptake inhibitor. Reboxetine inhibits metabolism of fluvoxamine Avoid concurrent use (manufacturers recommendation)... 

SSRIs ATOMOXETINE t plasma concentrations and risk of adverse effects (abdominal pain, vomiting, nausea, fatigue, irritability) Atomoxetine is a selective norepinephrine reuptake inhibitor, t plasma concentrations due to inhibition of CYP2D6 by fluoxetine and paroxetine (potent), fluvoxamine and sertraline (less potent) and escitalopram and citalopram (weak) Avoid concurrent use. The interaction is usually severe with fluoxetine and paroxetine... 

Unlike other agents approved for ADHD, atomoxetine does not have abuse potential and is not a scheduled substance Despite its name as a selective norepinephrine reuptake inhibitor, atomoxetine enhances both dopamine and norepinephrine in frontal cortex, presumably accounting for its therapeutic actions on attention and concentration... 

Preliminary studies and atomoxetine s known mechanism of action as a selective norepinephrine reuptake inhibitor suggest its efficacy as an antidepressant... 

Atomoxetine, a selective norepinephrine reuptake inhibitor, is the first nonstrmulant approved by the Food and Drug Administration (FDA) for the treatment of ADHD. In contrast to the stimulants, it has no apparent abuse potential and is not a controlled substance. Placebo-controlled, short-term trials (6 to 12 weeks) have shown that atomoxetine is effective in reducing ADHD symptoms in children, teens, and adults. It is not clear whether it is as effective as the stimulants, although one preliminary open study suggested comparable efficacy with methylphenidate. ... 

A critical part of the assessment must be to determine the patient s impairment at various times throughout the day to ensure that medication coverage overlaps with the time when the patient is most likely to benefit. As with all medication trials, it is important to start with a low dose of medication and keep increasing it slowly until the optimal risk-to-benefit ratio has been determined. Stimulant medication (methylphenidate, mixed amphetamine salts, and pemoline) and atomoxetine (a non-stimulant selective norepinephrine reuptake inhibitor, approved by the FDA for adult ADHD) are the first-line treatments of adult ADHD. Pemoline is not recommended as first-line treatment due to the risk of hepatoxicity. Stimulant drugs used to treat adults with ADHD are considered safe and effective, and have been well studied. There are several new long-acting formulations of... 

Nortriptyline, a tricyclic antidepressant (TCA), is a non-selective norepinephrine reuptake inhibitor, and long-term abstinence outcomes are not significantly different from bupropion. However, only NRT and bupropion are currently approved by the FDA for the treatment of tobacco dependence. ... 

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