| Title | The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson's disease. | | Author(s) | Scheller D, Ullmer C, Berkels R, Gwarek M, Lübbert H | | Institution | Pharmacology/Toxicology, Schwarz Biosciences GmbH, Alfred-Nobel-Strasse 10, 40789, Monheim, Germany, dieter.scheller@ucb-group.com. | | Source | Naunyn Schmiedebergs Arch Pharmacol 2008 Aug 14. | | Abstract | Rotigotine (Neupro(R)) 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 D(3) receptor (K (i) = 0.71 nM) with its affinities to other dopamine receptors being (K (i) in nM): D(4.2) (3.9), D(4.7) (5.9), D(5) (5.4), D(2) (13.5), D(4.4) (15), and D(1) (83). Significant affinities were also demonstrated at alpha-adrenergic (alpha(2B), K (i) = 27 nM) and serotonin receptors (5-HT(1A) K (i) = 30 nM). In newly developed reporter-gene assays for determination of functional activity, rotigotine behaved as a full agonist at dopamine receptors (rank order: D(3 )> D(2L )> D(1) = D(5 )> D(4.4)) with potencies 2,600 and 53 times higher than dopamine at dopamine D(3) and D(2L) receptors, respectively. At alpha-adrenergic sites, rotigotine acted as an antagonist on alpha(2B) receptors. At serotonergic sites, rotigotine had a weak but significant agonistic activity at 5-HT(1A) 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 D(3) receptor over D(2) and D(1) receptors. In addition, it exhibits interaction with D(4) and D(5) receptors, the role of which in relation to PD is not clear yet. Among non-dopaminergic sites, rotigotine shows relevant affinity to only 5-HT(1A) and alpha(2B) 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18704368 |
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