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 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.