Effect of low concentrations of apomorphine on parkinsonism in a randomized, placebo-controlled, crossover study

Arch Neurol. 2008 Feb;65(2):193-8. doi: 10.1001/archneurol.2007.58.


Objective: To determine whether low concentrations of a dopamine agonist worsen parkinsonism, which would suggest that activation of presynaptic dopamine autoreceptors causes a super-off state.

Design: Randomized, double-blind, placebo-controlled, crossover clinical trial.

Setting: Academic movement disorders center.

Patients: Patients with Parkinson disease and motor fluctuations.

Intervention: Fourteen patients with Parkinson disease and motor fluctuations were randomized to receive 1 of 6 possible sequences of placebo, low-dose (subthreshold) apomorphine hydrochloride, and high-dose (threshold to suprathreshold) apomorphine hydrochloride infusions. Subthreshold doses of apomorphine hydrochloride (12.5 microg/kg/h every 2 hours and 25 microg/kg/h every 2 hours), threshold to suprathreshold doses of apomorphine hydrochloride (50 microg/kg/h every 2 hours and 100 microg/kg/h every 2 hours), and placebo were infused for 4 hours daily for 3 consecutive days.

Main outcome measures: Finger and foot tapping rates.

Results: There was no decline in finger or foot tapping rates during the low-dose apomorphine hydrochloride infusions relative to placebo. The high-dose infusions increased foot tapping (P < .001) and trended toward increasing finger tapping compared with placebo infusions.

Conclusions: Subthreshold concentrations of apomorphine did not worsen parkinsonism, suggesting that presynaptic dopamine autoreceptors are not important to the motor response in moderate to advanced Parkinson disease. Trial Registration clinicaltrials.gov Identifier: NCT00472355.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / pharmacokinetics
  • Antiparkinson Agents / therapeutic use*
  • Apomorphine / administration & dosage
  • Apomorphine / pharmacokinetics
  • Apomorphine / therapeutic use*
  • Cross-Over Studies
  • Dopamine Agonists / administration & dosage
  • Dopamine Agonists / pharmacokinetics
  • Dopamine Agonists / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism
  • Psychomotor Performance
  • Receptors, Dopamine / metabolism
  • Severity of Illness Index
  • Treatment Outcome


  • Antiparkinson Agents
  • Dopamine Agonists
  • Receptors, Dopamine
  • Apomorphine

Associated data

  • ClinicalTrials.gov/NCT00472355