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

Robert A. Hauser, Laurence Salin, Nolwenn Juhel, Victor L. Konyago, Carmel Armon, Danny Bartel, Nicolaas I. Bohnen, Bruce Cleeremans, Cynthia Comella, Warren Davidson, J. Antonnelle De Marcaida, Anthony Dowel, Edward Drasby, Bradley Evans, Enrico Fazzini, Gerald Ferencz, Hubert Fernandez, Jeffrey Friedlander, Susanne Gazda, Mark GuttmanDavid Hart, Stuart Isaacson, Alan Jacobs, Joseph Jankovic, Danna Jennings, David King, Louis C. Kirby, Bruce Kohrman, Sandra Kostyk, Michael R. Liebowitz, Michael Lobatz, David Ira Margolin, Ekaterini Markopoulou, John M. Murphy, W. Alvin McElveen, Chi Kin Ng, Margarita Nunez, Sotiriof A. Parashos, John Porter, Emmanuelle Pourcher, Ali Rajput, Ralph Richter, David B. Ross, Harvey D. Schwartz, Carlos Singer, James Stevens, Jon Stoessl, Oksana Suchowersky, James P. Sutton, Mutaz Tabbaa, Daniel Truong, Paul Tuite, Roil I.Ann Wallis, Jeannette Wendt, Theresa Zesiewicz, Richard Zweig

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


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 performed a proof-of-concept, randomized, double-blind trial of NS 2330. Two hundred sixty-one subjects with PD < 5 years and not receiving dopaminergic treatment were randomly assigned to daily treatment with NS 2330 at 0.25 mg, 0.5 mg, 1.0 mg, or placebo. Adjusted mean difference in total Unified Parkinson's Disease Rating Scale (UPDRS) scores from baseline to week 14 was -0.7 (P = 0.64) in the 0.25-mg group, -1.3 (P = 0.41) in the 0.5-mg group, and -1.7 (P = 0.27) in the 1.0-mg group. The adjusted mean difference in total UPDRS score for the highest dose group (1.0 mg/day) was superior to placebo at week 6 (-3.1; P = 0.02), but this effect was not sustained. NS 2330 was generally well tolerated and the most commonly reported adverse events were constipation, insomnia, and dry mouth. Decreased body weight and elevated heart rate were common in the 1.0-mg dosage group. At the dosages tested, NS 2330 did not provide significantly greater benefit than placebo. It is possible that inhibition of dopamine reuptake alone does not provide clinical benefit in early PD, adequate inhibition of dopamine reuptake was not achieved in this study, or counter-vailing physiologic mechanisms offset the potential benefit.

Original languageEnglish (US)
Pages (from-to)359-365
Number of pages7
JournalMovement Disorders
Issue number3
StatePublished - Feb 15 2007
Externally publishedYes


  • Clinical trial
  • Dopamine reuptake inhibitor
  • Dopamine transporter
  • Monotherapy
  • NS 2330
  • Parkinson's disease
  • Tesofensine
  • Treatment

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)


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