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

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