title: Effects of dopaminergic treatment on striatal dopamine turnover in de novo Parkinson disease.
abstract: OBJECTIVE
  To evaluate the effects of levodopa and the dopamine D2 agonist cabergoline on striatal dopamine turnover estimated as the inverse of the effective dopamine distribution volume ratio (EDVR) measured by (18)F-dopa PET in de novo Parkinson disease (PD).
  
  
  METHODS
  Single-center, parallel-group, randomized, observer-blinded study of cabergoline (3 mg/day) and levodopa (300 mg/day) over 12 weeks in patients with de novo PD. Primary efficacy measure was the change of the side-to-side averaged putaminal EDVR comparing baseline and end-of-maintenance period.
  
  
  RESULTS
  Thirty-five out of 39 randomized patients were assigned to the primary efficacy analysis (cabergoline, n = 17; levodopa, n = 18). At the end of treatment period, mean EDVRs were significantly lower compared to baseline solely in the levodopa group (relative change -1.0 ± 13.0% in cabergoline [p = 0.525 when compared to baseline], -8.3 ± 11.8% in levodopa group [p = 0.006]) with a nonsignificant trend between groups (mean relative difference: 7.3% (95% confidence interval -1.2% to 15.8%; p = 0.091). There was significant clinical improvement in both groups at 12 weeks compared to baseline, but no significant differences between groups in clinical and PET secondary outcome measures. Both pharmacologic treatments and PET scanning were well-tolerated and safe.
  
  
  CONCLUSIONS
  Putaminal dopamine turnover is increased by levodopa treatment in de novo PD. The nonsignificant trend toward a larger influence by levodopa compared to cabergoline is supported by ancillary statistical analyses. This augmentation of early compensatory events by levodopa might contribute not only to its symptomatic effects, but also to its induction of motor complications.
authors.affiliation: Division of Neurodegenerative Diseases, Dresden University of Technology, Dresden, Germany. Alexander.Storch@neuro.med.tu-dresden.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Storch
authors.forename: Martin
authors.initials: M
authors.lastname: Wolz
authors.forename: Bettina
authors.initials: B
authors.lastname: Beuthien-Baumann
authors.forename: Matthias
authors.initials: M
authors.lastname: Löhle
authors.forename: Birgit
authors.initials: B
authors.lastname: Herting
authors.forename: Uta
authors.initials: U
authors.lastname: Schwanebeck
authors.forename: Liane
authors.initials: L
authors.lastname: Oehme
authors.forename: Jörg
authors.initials: J
authors.lastname: van den Hoff
authors.forename: Maria
authors.initials: M
authors.lastname: Perick
authors.forename: Xina
authors.initials: X
authors.lastname: Grählert
authors.forename: Jörg
authors.initials: J
authors.lastname: Kotzerke
authors.forename: Heinz
authors.initials: H
authors.lastname: Reichmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use; D000077465:Cabergoline; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use; D004873:Ergolines / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D011446:Prospective Studies; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D004873:Ergolines; D007980:Levodopa; D000077465:Cabergoline; D004298:Dopamine