Apomorphine Infusion and the Long-Duration Response to Levodopa in Advanced Parkinson's Disease

Abstract

The authors investigated the long-duration response to levodopa in advanced Parkinson's disease. Eight patients with advanced Parkinson's disease disabled by severe ON/OFF fluctuations treated by chronic daytime subcutaneous apomorphine infusion with supplemental oral levodopa were studied. On day 1, oral levodopa was withdrawn at 4:00 pm and on the following morning subcutaneous apomorphine infusion was continued at the same rate without levodopa therapy. While receiving apomorphine alone, seven of the eight patients turned ON, and their usual dyskinesias returned. The ON phase persisted for 60 to 100 minutes (mean, 185.7 minutes) but then, despite continued, constant-rate apomorphine infusion to stabilize plasma levels, switched to an OFF phase. The authors conclude that the clinical effect of apomorphine is sustained by levodopa long-duration response. This effect is probably the result of postsynaptic mechanisms. In patients with advanced Parkinson's disease, the long-duration response to levodopa is present although slightly diminished.

Motor features and response to oral levodopa in patients with Parkinson’s disease under continuous dopaminergic infusion or deep brain stimulation

“…This finding is in keeping with previous studies reporting that STN DBS can provide greater reduction in dopaminergic medications and ÔoffÕ time improvement than apomorphine infusion [24,25] and that jejunal levodopa can be more efficacious than apomorphine infusion to control motor fluctuations [26]. The present data are also in keeping with a previous report that apomorphine monotherapy fails to keep patients with PD in the ÔonÕ state after withdrawal of oral levodopa [27] and that only a minority of patients with continuous apomorphine infusions can withdraw all other medications [28].…”

Acute vs chronic effects of l-dopa on bladder function in patients with mild Parkinson disease

“…26,27 This suggests that postsynaptic changes may be concomitantly or exclusively involved in the origin of LDR. It has been recently suggested that changes of the intracellular mechanism of D1 transmission due to prolonged therapy may be largely responsible of the appearance of dyskinesia.…”

Concomitant short‐ and long‐duration response to levodopa in the 6‐OHDA‐lesioned rat: a behavioural and molecular study

“…The phenomenology of this improvement and its further decay when levodopa is stopped resembles the LDR to levodopa. These results suggest that the motor effect induced by the test dose of levodopa is sustained by levodopa LDR as has been described for the clinical effect of apomorphine in patients with advanced PD (Stocchi et al ., 2003).…”