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Steven A. Gunzler, MD; Caroline Koudelka, MPH; Nichole E. Carlson, PhD; Misha Pavel, PhD; John G. Nutt, MD

Arch Neurol. 2008;65(2):193-198.

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 µg/kg/h every 2 hours and 25 µg/kg/h every 2 hours), threshold to suprathreshold doses of apomorphine hydrochloride (50 µg/kg/h every 2 hours and 100 µg/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

Author Affiliations: Parkinson's Disease Research, Education, and Clinical Center, Portland VA Medical Center, Portland, Oregon (Drs Gunzler and Nutt); and Parkinson Center of Oregon (Drs Gunzler and Nutt), Oregon Clinical and Translational Research Institute (Ms Koudelka), Division of Biostatistics, Department of Public Health & Preventive Medicine (Dr Carlson), and Department of Biomedical Engineering (Dr Pavel), Oregon Health & Sciences University, Portland. Dr Gunzler is now with the Movement Disorders Center, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio.

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