Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson's disease

  title={Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson's disease},
  author={Robert A. Hauser and Laurence Salin and Nolwenn Juhel and Victor L Konyago},
  journal={Movement Disorders},
The objective of this study was to evaluate the efficacy and safety of three daily dosages of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) compared to placebo as monotherapy in early Parkinson's disease (PD). In MPTP (1‐methyl 4‐phenyl‐tetrahydropyridine 1,2,3,6)‐lesioned marmosets, dopamine reuptake inhibitors have been demonstrated to reverse parkinsonian signs without evoking established dyskinesia. NS 2330 inhibits reuptake of dopamine, serotonin, and norepinephrine. We… 
Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS Study.
Patients with PD in advanced stages showed modest improvements in UPDRS subscale II plus subscale III total score and in off time when treated with tesofensine, but a dose-response relationship could not be established for efficacy, while adverse drug reactions tended to be more frequent at higher dosages.
Subjective and Objective Effects of the Novel Triple Reuptake Inhibitor Tesofensine in Recreational Stimulant Users
The study results show that the effects of D‐amphetamine were significantly greater than those of placebo on all primary and secondary subjective measures and tesofensine is therefore unlikely to be recreationally abused.
Dopamine Reuptake Inhibitors in Parkinson’s Disease: A Review of Nonhuman Primate Studies and Clinical Trials
Alternative approaches to dopamine replacement in parkinsonism generally and to wearing-off and dyskinesia are urgently needed, and a hypothesis as to how tailoring the selectivity of DAT inhibitors might maximize the benefits of Dat inhibition in PD is proposed.
Experimental Dopamine Reuptake Inhibitors in Parkinson’s Disease: A Review of the Evidence
  • T. Müller
  • Biology, Psychology
    Journal of experimental pharmacology
  • 2021
Possible benefits of dopamine reuptake inhibition for the treatment of PD are discussed and the evidence for a preventive and beneficial, symptomatic effect of MRT inhibition on motor and non-motor complications will become more likely.
Monoamine Reuptake Inhibitors in Parkinson's Disease
This review article summarises all of the available literature on use of 50 MAUIs in PD and concludes that selective serotonin transporter (SERT), selective noradrenaline transporter (NET), and dual SERT/NET inhibitors are effective against PD depression.
Triple reuptake inhibitors for treating subtypes of major depressive disorder: the monoamine hypothesis revisited
This article reviews the development of new broad-spectrum antidepressants, the triple reuptake inhibitors, which also increase brain dopamine levels and proposes a hypothetical model: ‘the monoamine hypothesis revisited’ to predict what kind of pharmacological treatment will be effective in the different subtypes of depression.
A New Class of Antidepressant Drugs in the Treatment of Psychiatric Disorders: The Triple Reuptake Inhibitors
Since TRIs simultaneously enhance extracellular levels of 5-HT, NE and DA neurotransmissions in various brain regions, this class of antidepressants could exert their therapeutic activity by treating more symptoms of MD and/or by attenuating some side effects of these agents.
Prospect of a dopamine contribution in the next generation of antidepressant drugs: the triple reuptake inhibitors.
This review synthetizes the pertinent litterature, focusing on the contribution of DA, to illustrate the rationale for designing improved antidepressants.
Monoamine Transporter Occupancy of a Novel Triple Reuptake Inhibitor in Baboons and Humans Using Positron Emission Tomography
GSK1360707 dose-dependently blocked the signal of SERT, DAT, and NET-selective PET ligands, confirming its penetration across the blood-brain barrier and blockade of all three monoamine transporters in vivo.


Effect of monoamine reuptake inhibitor NS 2330 in advanced Parkinson's disease
The present results failed to support the usefulness of dopamine reuptake inhibition in the treatment of advanced Parkinson's disease.
The monoamine reuptake blocker brasofensine reverses akinesia without dyskinesia in MPTP‐treated and levodopa‐primed common marmosets
The ability of brasofensine to produce a prolonged and naturalistic antiparkinsonian response without eliciting dyskinesia after previous L‐dopa priming may relate to actions on D1 receptor‐linked pathways.
Brasofensine Treatment for Parkinson's Disease in Combination with Levodopa/Carbidopa
Brasofensine was safe and well tolerated in the patient cohort studied at daily doses of up to 4 mg, and based on the motor performance subscale of the Unified Parkinson's Disease Rating Scale, no change in patient disability was observed at any dose level.
Sibutramine: A Serotonin–Norepinephrine Reuptake-Inhibitor for the Treatment of Obesity
Based on anorectic efficacy data, sibutramine, a serotonin–norepinephrine reuptake-inhibitor, is a viable therapeutic option for the treatment of obesity.
The dopamine transporter: Importance in Parkinson's disease
Observations indicate that the residual DAT is functional in PD and is a potential target for symptomatic therapy of PD, particularly doses at threshold for clinical effects.
NS-2330 (Neurosearch).
  • U. Thatte
  • Psychology
    Current opinion in investigational drugs
  • 2001
NeuroSearch is developing NS-2330, a compound that increases the activity of dopamine, norepinephrine and acetylcholine, as a potential therapy for Alzheimer's disease (AD) and Parkinson's disease
Dopamine, but Not Norepinephrine or Serotonin, Reuptake Inhibition Reverses Motor Deficits in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Primates
There seems to be no role for NE or 5-HT reuptake inhibitors, and they may impair antiparkinsonian activity mediated through dopaminergic mechanisms, which may be useful in the treatment of the motor symptoms of Parkinson's disease.
Profound neuronal plasticity in response to inactivation of the dopamine transporter.
It is interesting to consider that the switch to a dopamine-deficient, but functionally hyperactive, mode of neurotransmission observed in mice lacking the DAT may represent an extreme example of neuronal plasticity resulting from long-term psychostimulant abuse.