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.


METHODS
Randomized, double-blind, placebo-controlled, crossover clinical trial.


METHODS
Academic movement disorders center.


METHODS
Patients with Parkinson disease and motor fluctuations.


METHODS
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.


METHODS
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.
Gunzler
Steven A
SA
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
Koudelka
Caroline
C
Carlson
Nichole E
NE
Pavel
Misha
M
Nutt
John G
JG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001058:Apomorphine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018592:Cross-Over Studies; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D011597:Psychomotor Performance; D011954:Receptors, Dopamine / Q000378:metabolism; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D001058:Apomorphine