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

Author(s): Gunzler SA, Koudelka C, Carlson NE, Pavel M, Nutt JG

Affiliation(s): Movement Disorders Center, Neurological Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, 11100 Euclid Ave, Cleveland, OH 44106, USA. steven.gunzler@uhhospitals.org

Publication date & source: 2008-02, Arch Neurol., 65(2):193-8.

Publication type: Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

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.