The development of tolerance to dopaminergic drugs may be important in
the long-term therapy of Parkinson's disease. In this study, we sough
t to determine whether tolerance developed during infusions of apomorp
hine and if there was evidence of any dose dependency. Eight patients
with Parkinson's disease received 4- to 6-h infusions of apomorphine a
t low, medium, and high rates on consecutive days. Before and after ea
ch infusion, test boluses of apomorphine were administered to measure
sensitivity to the drug. The duration of motor effects after the posti
nfusion boluses were reduced in comparison to those of the preinfusion
boluses, indicating that tolerance developed during the infusions. Th
e infusion rate did not affect the responses to the postinfusion test
boluses. Our observations indicate that tolerance develops to the anti
parkinsonian effect of apomorphine after several hours of its constant
infusion, but is not influenced by the dose of drug administered.