The duration of the motor response to apomorphine boluses is conditioned by the length of a prior infusion in Parkinson's disease.

"Pulsatile" administration of levodopa has been invocated a relevant factor for motor fluctuations in Parkinson's disease (PD). We studied dopaminergic sensitivity to apomorphine in 10 parkinsonian patients with motor fluctuations. Patients were tested as follows: the minimal effective dose of apomorphine (MED-1) was administered in the morning to induce an on response. Fifteen minutes after this motor response had disappeared, an apomorphine infusion was initiated and maintained to ensure on periods of three different durations on different days. Infusion lasted for approximately 30, 60 and 90 minutes. Subsequently, the infusion was stopped, and after 15 minutes in the off state, a second bolus of apomorphine (MED-2) was given. The mean infusion doses were 49.2 +/- 5.4, 108.4 +/- 10.3, and 150 +/- 8.2 mg. These elicited on periods of 48.2 +/- 4.1, 110 +/- 4.5, and 195 +/- 3.8 minutes. The MED-2 elicited on responses with a duration of 30 +/- 4.5, 18.4 +/- 3.2, and 11.2 +/- 4.1 minutes. The duration of the on response induced by the apomorphine infusions correlated inversely (P < 0.01) with the on induced by the MED-2 of apomorphine. Our findings indicate that a continuous dopaminergic stimulus may induce pharmacodynamic changes associated with tolerance in PD patients.