title: In vivo dopamine agonist properties of rotigotine: Role of D1 and D2 receptors.
abstract: Rotigotine acts in vitro as a full agonist of dopamine D1 receptors at concentrations almost superimposable to those at which it acts on D2 receptors. However in vivo evidence of the differences between the agonist activity of rotigotine at D1 receptors from that on the D2 receptors has not been provided yet. In order to test the ability of rotigotine to stimulate dopamine D1 and D2 receptors in vivo, we studied the effect of SCH39166 and eticlopride, selective dopamine D1 and D2/D3 receptor antagonists respectively, on rotigotine-induced contralateral turning behavior in 6-hydroxydopamine lesioned rats. Furthermore, the expression of the immediate-early gene c-fos in the caudate-putamen, was evaluated. As a comparison, we tested the D2/D3 agonist pramipexole. In primed rats, rotigotine (0.035, 0.1 and 0.35mg/kg) induced dose-dependent contralateral turning. Turning induced by 0.1mg/kg of rotigotine was reduced by pretreatment with the D1 antagonist SCH39166 and the D2 antagonist eticlopride. In drug-naive rats, rotigotine was less effective in eliciting turning but SCH39166 still reduced turning induced by rotigotine (0.35mg/kg). Pramipexole induced contralateral turning only in primed rats. SCH39166 potentiated and eticlopride abolished pramipexole-induced turning. Rotigotine induced Fos expression in the caudate-putamen and SCH39166 completely blocked it. Pramipexole failed to induce Fos. These results indicate that rotigotine acts in vivo as an agonist of D1 and D2 receptors while pramipexole is devoid of D1 activity in vivo. Given their differing DA receptor profiles, rotigotine and pramipexole might differ in their spectrum of application to the therapy of Parkinson's disease.
authors.affiliation: Department of Biomedical Sciences, Neuropsychopharmacology Section, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy. Electronic address: sfenu@unica.it.
authors.forename: Sandro
authors.initials: S
authors.lastname: Fenu
authors.affiliation: Department of Biomedical Sciences, Neuropsychopharmacology Section, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Espa
authors.affiliation: National Research Council of Italy, Neuroscience Institute, Cagliari Section, Cagliari, Italy.
authors.forename: Augusta
authors.initials: A
authors.lastname: Pisanu
authors.affiliation: Department of Biomedical Sciences, Neuropsychopharmacology Section, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy; National Research Council of Italy, Neuroscience Institute, Cagliari Section, Cagliari, Italy. Electronic address: gadichia@tiscali.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Di Chiara
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D052160:Benzothiazoles / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D000077487:Pramipexole; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D000077487:Pramipexole; C047508:rotigotine; D016627:Oxidopamine; D004298:Dopamine
keywords: Dopamine D(1) receptor; Dopamine D(2) receptor; Eticlopride (PubChem CID: 6917728); Parkinson's disease; Pramipexole; Pramipexole dihydrochloride (PubChem CID: 119569); Rotigotine; Rotigotine hydrochloride (PubChem CID: 180335); SCH 39166 (PubChem CID: 16759171); Turning behavior