title: Occupancy of pramipexole (Sifrol) at cerebral dopamine D2/3 receptors in Parkinson's disease patients.
abstract: Whereas positron emission tomography (PET) with the antagonist ligand [(18)F]fallypride reveals the composite of dopamine D2 and D3 receptors in brain, treatment of Parkinson's disease (PD) patients with the D3-prefering agonist pramipexole should result in preferential occupancy in the nucleus accumbens, where the D3-subtype is most abundant. To test this prediction we obtained pairs of [(18)F]fallypride PET recordings in a group of nine PD patients, first in a condition of treatment as usual with pramipexole (ON-Sifrol; 3 × 0.7 mg p.d.), and again at a later date, after withholding pramipexole 48-72 h (OFF-Sifrol); in that condition the serum pramipexole concentration had declined by 90% and prolactin levels had increased four-fold, in conjunction with a small but significant worsening of PD motor symptoms. Exploratory comparison with historical control material showed 14% higher dopamine D2/3 availability in the more-affected putamen of patients OFF medication. On-Sifrol there was significant (p ˂ 0.01) occupancy at [(18)F]fallypride binding sites in globus pallidus (8%) thalamus (9%) and substantia nigra (19%), as well as marginally significant occupancy in frontal and temporal cortex of patients. Contrary to expectation, comparison of ON- and OFF-Sifrol results did not reveal any discernible occupancy in nucleus accumbens, or elsewhere in the extended striatum; present methods should be sensitive to a 10% change in dopamine D2/3 receptor availability in striatum; the significant findings elsewhere in the basal ganglia and in cerebral cortex are consistent with a predominance of D3 receptors in those structures, especially in substantia nigra, and imply that therapeutic effects of pramipexole may be obtained at sites outside the extended striatum.
authors.affiliation: Department of Neurology, Ludwig-Maximilians University of Munich, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Deutschländer
authors.affiliation: Department of Nuclear Medicine, Eberhard-Karls-University of Tübingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: la Fougère
authors.affiliation: Department of Neurology, Ludwig-Maximilians University of Munich, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Boetzel
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians University of Munich, Germany.
authors.forename: Nathalie L
authors.initials: NL
authors.lastname: Albert
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians University of Munich, Germany.
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Gildehaus
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians University of Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians University of Munich, Germany.
authors.forename: Guoming
authors.initials: G
authors.lastname: Xiong
authors.affiliation: Department of Neuropsychiatry and Psychosomatic Medicine, Rikshospitalet, University of Oslo, Oslo, Norway; School of Psychology and Counselling, Institute of Health and Biomedical Innovation, Faculty of Health, Queensland University of Technology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
mesh_terms: D000368:Aged; D001549:Benzamides / Q000494:pharmacology; D052160:Benzothiazoles / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D049268:Positron-Emission Tomography; D000077487:Pramipexole; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D050637:Receptors, Dopamine D3 / Q000187:drug effects*
chemical_list: D001549:Benzamides; D052160:Benzothiazoles; C581293:DRD2 protein, human; C493593:DRD3 protein, human; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D019788:Fluorodeoxyglucose F18; D000077487:Pramipexole; C574003:fallypride
keywords: Agonist; Dopamine receptors; Fallypride; Occupancy; Parkinson's disease; Pet; Pramipexole