Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 379, Issue 1, pp 73–86 | Cite as

The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson’s disease

  • Dieter Scheller
  • Christoph Ullmer
  • Reinhard Berkels
  • Mirella Gwarek
  • Hermann Lübbert
Original Article

Abstract

Rotigotine (Neupro®) is a non-ergoline dopamine agonist developed for the once daily treatment of Parkinson’s disease (PD) using a transdermal delivery system (patch) which provides patients with the drug continuously over 24 h. To fully understand the pharmacological actions of rotigotine, the present study determined its extended receptor profile. In standard binding assays, rotigotine demonstrated the highest affinity for dopamine receptors, particularly the dopamine D3 receptor (Ki = 0.71 nM) with its affinities to other dopamine receptors being (Ki in nM): D4.2 (3.9), D4.7 (5.9), D5 (5.4), D2 (13.5), D4.4 (15), and D1 (83). Significant affinities were also demonstrated at α-adrenergic (α2B, Ki = 27 nM) and serotonin receptors (5-HT1AKi = 30 nM). In newly developed reporter-gene assays for determination of functional activity, rotigotine behaved as a full agonist at dopamine receptors (rank order: D3 > D2L > D1 = D5 > D4.4) with potencies 2,600 and 53 times higher than dopamine at dopamine D3 and D2L receptors, respectively. At α-adrenergic sites, rotigotine acted as an antagonist on α2B receptors. At serotonergic sites, rotigotine had a weak but significant agonistic activity at 5-HT1A receptors and a minor or nonexistent activity at other serotonin receptors. Thus, in respect to PD, rotigotine can be characterized as a specific dopamine receptor agonist with a preference for the D3 receptor over D2 and D1 receptors. In addition, it exhibits interaction with D4 and D5 receptors, the role of which in relation to PD is not clear yet. Among non-dopaminergic sites, rotigotine shows relevant affinity to only 5-HT1A and α2B receptors. Further studies are necessary to investigate the contribution of the different receptor subtypes to the efficacy of rotigotine in Parkinson’s disease and possible other indications such as restless legs syndrome.

Keywords

Rotigotine Parkinson’s disease Restless legs Dopamine receptor agonist Serotonin receptor Adrenaline receptor 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Dieter Scheller
    • 1
    • 2
  • Christoph Ullmer
    • 3
    • 5
  • Reinhard Berkels
    • 4
  • Mirella Gwarek
    • 3
  • Hermann Lübbert
    • 3
  1. 1.Pharmacology/ToxicologySchwarz Biosciences GmbHMonheimGermany
  2. 2.CNS Pharmacology, UCB Pharma SA, Chemin du ForiestBraine l’AlleudBelgium
  3. 3.Biofrontera Pharmaceuticals GmbHHemmelrather Weg 201LeverkusenGermany
  4. 4.Schwarz Biosciences GmbHMonheimGermany
  5. 5.F.Hoffman-La Roche AG, GrenzacherstrasseBaselSwitzerland

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