DA reuptake

Antidepressants (MAOIs, TCAs, 5-HT and/or NE and/or DA reuptake inhibitors, 5-HT antagonists)... 

Agents that increase neurottansmitter activity are used for the treatment of depression (e.g, 5-HT and DA reuptake inhibitors and MAOIs). 

Bupropion s most potent neurochemical action is blockade of DA reuptake it blocks the reuptake of NE to a lesser extent. 

The serotonin-norepinephrine reuptake inhibitors include venlafaxine and duloxetine. Venlafaxine is an inhibitor of 5-HT and NE reuptake and a weak inhibitor of DA reuptake. Desvenlafaxine (Pristiq) was recently approved by the FDA. The dose is 50 mg once daily. 

Considerable effort in the field of monoamine reuptake inhibitors is focused on improving antidepressant efficacy since 30-40% of patients do not respond to treatment with currently available agents [6,7], An additional major objective is to enhance the onset of action. Current antidepressants typically require 2-6 weeks of treatment before clinical efficacy is seen [6]. Clinical trials exploring augmentation strategies, in which a DA reuptake inhibitor or a dual NE/DA reuptake inhibitor is combined with an SSRI, have resulted in improved efficacy in depressed patients refractory to SSRI treatment alone [4,5]. The improved results from clinical trials such as these serve to justify the considerable focus on the development of inhibitors that simultaneously block the reuptake of 5-HT, NE and DA. 

Although it is often classified as a SNRI, sibutramine (26) is metabolized in vivo to produce metabolites that have varying degrees of inhibition of NE, 5-HT and DA reuptake [83,84]. It has been approved for the control of obesity in the U.S. and many other countries. 

Sertraline Blocks DA reuptake H Serotonin Parkinson s disease ADHD Depression... 

The development of GBR 12909, which had shown preliminary evidence of antidepressant efficacy (Fensbo et al. 1990], was discontinued because of lack of efficacy in a subsequent placebo-controlled trial. GBR 12909 is the most potent and selective inhibitor of DA reuptake to be tested in humans (Sogaard et al. 1990], and its affinity for the human DA transporter is similar to that of nomifensine (Table 14-2]. It appears to block DA reuptake by binding to the DA binding site on the transporter protein, thereby blocking... 

Amineptine is only about 10 times less effective in inhibiting NA than DA reuptake in vitro and is also markedly less potent at DA sites than is GBR 12909 [Garattini and Mennini 1989). Mesolimbic Dj autoreceptor sensitivity in mice was reduced by long-term administration of amineptine [Chag-raoui et al. 1990), an effect common to many antidepressants [Willner et al. 

Dopamine reuptake can be inhibited specifically by benztropine (4.80), an anticholinergic drug, as well as by amphetamines. Several specific DA reuptake inhibitors have been discovered, such as tandamine (4.81), bupropion (4.82), and nomifensine (4.83), which are all potent antidepressants. Tandamine also inhibits NE uptake. 

However, among the many possibilities that present themselves, compounds that directly block the DA reuptake transporter but that have a much slower onset of action and much longer duration of action seem plausible candidates, by analogy to cocaine s action as a DA reuptake transporter or carrier blocker. My colleagues and I hypothesize that slower onset and longer duration of action are critical features of such... 

Preliminarily, the data seem highly promising that this may be a useful approach to the previously intractable problem of efficacious pharmacotherapies for cocaine addiction. In in-vitro receptor binding studies and in-vitro DA reuptake carrier binding studies (Froimowitz, Wu, and Spealman 1996), compounds from the first chemical series designed and... 

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