Serotonin-noradrenaline-dopamine reuptake inhibitor

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Serotonin-norepinephrine-dopamine-reuptake-inhibitors (SNDRI) are a class of psychoactive antidepressants. They act upon neurotransmitters in the brain, namely, serotonin, norepinephrine and dopamine. These three biogenic monoamines are associated with depression and increasing the availability in the brain is used to treat the disease.

SNDRIs are so-called triple reuptake inhibitors, which elevate extracellular plasma concentrations of all three monoamine neurotransmitters, serotonin, norepinephrine and dopamine in the synaptic cleft. These compounds show high potency but low selectivity between the different monoamine transporter proteins. No SNDRIs are yet on the market, although the first of these agents tesofensine is currently in clinical trials,[1][2] and other compounds such as brasofensine[3] and GlaxoSmithKline's NS2359[4] are under development.

It should be noted that some SNRI drugs such as Venlafaxine (Effexor) and Sibutramine (Meridia/Reductil) are known to weakly inhibit the reuptake of dopamine at high doses, and so while these drugs are selective for the serotonin and noradrenaline transporters at normal doses, they can start to act as SNDRIs when taken at doses above the normal therapeutic range.

References

  1. "Tesofensine". Retrieved 2007-08-20.
  2. Lehr T, Staab A, Tillmann C; et al. (2007). "Population pharmacokinetic modelling of NS2330 (tesofensine) and its major metabolite in patients with Alzheimer's disease". British journal of clinical pharmacology. 64 (1): 36–48. doi:10.1111/j.1365-2125.2007.02855.x. PMID 17324246.
  3. Pearce RK, Smith LA, Jackson MJ, Banerji T, Scheel-Krüger J, Jenner P (2002). "The monoamine reuptake blocker brasofensine reverses akinesia without dyskinesia in MPTP-treated and levodopa-primed common marmosets". Mov. Disord. 17 (5): 877–86. doi:10.1002/mds.10238. PMID 12360536.
  4. http://www.neurosearch.com/Default.aspx?ID=117



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