Name: Rotigotine
Synonyms: Neupro
Chemical Name: (S)-6-[Propyl(2-thiophen-2-ylethyl)amino]-5,6,7,8- tetrahydronaphthalen-1-ol
Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: UCB S.A.
Approved for: Parkinson's disease, Restless Leg Syndrome


This dopamine receptor agonist is approved to treat Parkinson’s disease and restless legs syndrome in Europe and the United States. It is formulated as a once-daily transdermal patch, in doses from 1 to 8 mg. Side effects include dyskinesia, constipation, nausea, dizziness, fatigue, insomnia, sleepiness, confusion, and hallucinations. Psychosis and impulse control disorders like pathological gambling are rare but serious side effects (Rotigotine, 2017).

In Alzheimer’s disease, deficits in dopamine signaling may contribute independently to cognitive decline. Decrements in executive function associated with diminished frontal cortical activity further diminished daily function, separate from memory loss. A group in Rome has investigated rotigotine’s effect on cortical function and plasticity in people with Alzheimer’s by using repetitive transcranial magnetic stimulation (rTMS). The drug reportedly upped cortical excitability and cholinergic transmission, reversing impairments in LTP-like cortical plasticity in these patients. In a small study of 30 people, rotigotine treatment for 24 weeks was reported to improve scores on the MMSE and the Frontal Assessment Battery (FAB), which tests cognitive functions related to prefrontal cortical activity (Martorana et al., 2013; Koch et al., 2014).


From June 2016 to December 2018, the investigators conducted a single-center, double-blind Phase 2 trial of rotigotine added on to acetylcholinesterase inhibitor therapy in mild to moderate Alzheimer’s. The trial enrolled 94 people with probable AD, CDR of 0.5 or 1, and MMSE scores between 18 and 24. Treatment consisted of a 2 mg rotigotine transdermal patch daily for one week, followed by 4 mg daily for 23 weeks, or a placebo patch for 24 weeks. All took a stable dose of donepezil, galantamine, or rivastigmine. The primary outcome was change in ADAS-Cog over 24 weeks; secondary outcomes included change in the FAB, the ADCS-Activities of Daily Living, the Neuropsychiatric Inventory, and cortical activity measured by transcranial magnetic stimulation combined with encephalography (TMS-EEG). 

The trial was negative on the primary endpoint, with no difference between groups on the ADAS-Cog. The treated group appeared to benefit on two secondary outcomes. Scores on the FAB rose by 0.48 points with rotigotine versus a 0.66-point decrease on placebo. The ADCS-ADL worsened by 3.32 points with rotigotine versus 7.24 for placebo. The NPI stayed unchanged in either group. EEG measures indicated increased prefrontal cortical activity in the rotigotine but not placebo groups. More people on rotigotine had adverse events; 11 dropped out compared with five on placebo. Side effects on rotigotine included nausea and dizziness in three people, allergic reactions to the patch in two, and visual hallucinations, pneumonia, sleep disorders, and anxiety in one person each (Koch et al., 2020). 

For more on this trial, see For all rotigotine trials, see

Last Updated: 17 Jul 2020


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Paper Citations

  1. . Effect of Rotigotine vs Placebo on Cognitive Functions Among Patients With Mild to Moderate Alzheimer Disease: A Randomized Clinical Trial. JAMA Netw Open. 2020 Jul 1;3(7):e2010372. PubMed.
  2. Rotigotine. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, Jul 21, 2017
  3. . Dopamine D(2)-agonist Rotigotine effects on cortical excitability and central cholinergic transmission in Alzheimer's disease patients. Neuropharmacology. 2013 Jan;64(1):108-13. PubMed.
  4. . Dopaminergic modulation of cortical plasticity in Alzheimer's disease patients. Neuropsychopharmacology. 2014 Oct;39(11):2654-61. Epub 2014 May 26 PubMed.

External Citations


Further Reading


  1. . Tolerability of non-ergot oral and transdermal dopamine agonists in younger and older Parkinson's disease patients: an European multicentre survey. J Neural Transm (Vienna). 2020 Jun;127(6):875-879. Epub 2020 May 5 PubMed.
  2. . Once-Weekly Subcutaneous Delivery of Polymer-Linked Rotigotine (SER-214) Provides Continuous Plasma Levels in Parkinson's Disease Patients. Mov Disord. 2020 Jun;35(6):1055-1061. Epub 2020 Apr 6 PubMed.
  3. . Current Status and Challenges in Rotigotine Delivery. Curr Pharm Des. 2020;26(19):2222-2232. PubMed.
  4. . Pharmacological Management of Lewy Body Dementia: A Systematic Review and Meta-Analysis. Am J Psychiatry. 2015 Aug 1;172(8):731-42. Epub 2015 Jun 18 PubMed.
  5. . Available and future treatments for atypical parkinsonism. A systematic review. CNS Neurosci Ther. 2019 Feb;25(2):159-174. Epub 2018 Oct 7 PubMed.
  6. . Non-ergot dopamine agonist rotigotine as a promising therapeutic tool in atypical parkinsonism syndromes: a 24 months pilot observational open-label study. Neuropharmacology. 2014 Oct;85:284-9. Epub 2014 Jun 7 PubMed.