title: Rotigotine is a potent agonist at dopamine D1 receptors as well as at dopamine D2 and D3 receptors.
abstract: OBJECTIVE
  Rotigotine acts as a dopamine receptor agonist with high affinity for the dopamine D2, D3, D4 and D5 receptors but with a low affinity for the dopamine D1 receptor. We have investigated this further in radioligand binding and functional studies and compared the profile of rotigotine with that of other drugs used in the treatment of Parkinson's disease (PD).
  
  
  METHODS
  The binding of rotigotine to human dopamine D1, D2, D3, D4 and D5 receptors was determined in radioligand binding studies using [(3)H]rotigotine and compared with that of standard antagonist radioligands. Functional interactions of rotigotine with human dopamine receptors was also determined.
  
  
  RESULTS
  [(3)H]rotigotine can be used as an agonist radioligand to label all dopamine receptor subtypes and this can be important to derive agonist affinity estimates. Rotigotine maintains this high affinity in functional studies at all dopamine receptors especially D1, D2 and D3 receptors and, to a lesser extent, D4 and D5 receptors. Rotigotine, like apomorphine but unlike ropinirole and pramipexole, was a potent agonist at all dopamine receptors.
  
  
  CONCLUSIONS
  Rotigotine is a high-potency agonist at human dopamine D1, D2 and D3 receptors with a lower potency at D4 and D5 receptors. These studies differentiate rotigotine from conventional dopamine D2 agonists, used in the treatment of PD, such as ropinirole and pramipexole which lack activity at the D1 and D5 receptors, but resembles that of apomorphine which has greater efficacy in PD than other dopamine agonists but has suboptimal pharmacokinetic properties.
authors.affiliation: UCB BioPharma SPRL, Chemin de Foriest, Braine-l'Alleud, Belgium.
authors.forename: Martyn
authors.initials: M
authors.lastname: Wood
authors.forename: Vanessa
authors.initials: V
authors.lastname: Dubois
authors.forename: Dieter
authors.initials: D
authors.lastname: Scheller
authors.forename: Michel
authors.initials: M
authors.lastname: Gillard
mesh_terms: D002460:Cell Line; D018491:Dopamine Agonists / Q000494:pharmacology*; D006801:Humans; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine