title: Striatal Dopamine Transporter Modulation After Rotigotine: Results From a Pilot Single-Photon Emission Computed Tomography Study in a Group of Early Stage Parkinson Disease Patients.
abstract: BACKGROUND
  Several in vitro data have reported negative interference by dopamine-agonists on the expression of dopamine transporter (DAT), whereas the majority of imaging studies have shown that neither L-dopa nor dopamine-agonists interfere with DAT availability. As yet, there are no in vivo studies on DAT expression after treatment with rotigotine.
  
  
  METHODS
  We evaluated presynaptic nigrostriatal function in 8 patients with de novo Parkinson disease (age, 59 ± 6.2 years; male/female sex, 5/3) using 123-I- N-ω-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophenyl)nortropane (FP-CIT) single-photon emission computed tomography before and after 3 months of treatment with rotigotine (mean dose, 7.75 ± 1.98 mg). For data analysis, specific (left and right caudate, left and right putamen) to nonspecific (occipital cortex) binding ratios, putamen-to-caudate ratios, and asymmetry indices were calculated.
  
  
  RESULTS
  After rotigotine, motor symptoms improved in all patients (Unified Parkinson Disease Rating Scale III mean score, 11.88 ± 2.59 vs 7.63 ± 1.92 on therapy; P = 0.0022). Striatal FP-CIT levels showed a significant improvement in every patient at the follow-up scan. Comparisons between before and after treatment in the whole group revealed a significant improvement in FP-CIT uptake in both caudate and putamen (P < 0.001 in each nucleus). Putamen-to-caudate ratio and asymmetry indices did not show any significant difference before and after treatment.
  
  
  CONCLUSIONS
  Although the study population was small, we found DAT overexpression after chronic treatment with rotigotine, presumably related to its pharmacological profile. The DAT upregulation by rotigotine in an opposite direction with respect to early Parkinson disease compensatory mechanisms might reduce the risk of dyskinesia, but it could imply less motor benefit because of less stimulation by the dopamine itself on dopaminergic receptors.
authors.affiliation: *Department of Clinical and Experimental Medicine, University of Pisa; and †Nuclear Medicine Unit, Fondazione Toscana "G. Monasterio," Pisa, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Rossi
authors.forename: Dario
authors.initials: D
authors.lastname: Genovesi
authors.forename: Paolo
authors.initials: P
authors.lastname: Marzullo
authors.forename: Assuero
authors.initials: A
authors.lastname: Giorgetti
authors.forename: Elena
authors.initials: E
authors.lastname: Filidei
authors.forename: Giovanni Umberto
authors.initials: GU
authors.lastname: Corsini
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Bonuccelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Ceravolo
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000187:drug effects; D018491:Dopamine Agonists / Q000627:therapeutic use*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D010865:Pilot Projects; D011446:Prospective Studies; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D014326:Tropanes / Q000493:pharmacokinetics
chemical_list: D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; C047508:rotigotine