Long‐duration response to levodopa influences the pharmacodynamics of short‐duration response in Parkinson's disease

Abstract

The long-duration response (LDR) to chronic levodopa treatment may mask the short-duration response (SDR) to a single dose of the drug in Parkinson's disease (PD). As a result, the measurement of SDR may be inaccurate for establishing levodopa dosing regimen in individual patients. To evaluate the possible contamination of SDR by LDR, we investigated in 16 patients with PD the characteristics of SDR to a single dose of levodopa administered after a prolonged washout from chronic therapy and after a 15-day treatment period with levodopa. Levodopa treatment produced a sustained LDR, and the SDR, measured on the 15th day of treatment, had lower magnitude and shorter duration than the response recorded after washout. Moreover, after treatment, SDR did not vary between patients with mild and severe PD, whereas, after washout, severely affected patients had larger but shorter SDR than mildly affected patients. The evaluation of SDR without the interference of LDR is critical in defining the characteristics of the therapeutic response to levodopa.

Beta Oscillatory Activity in the Subthalamic Nucleus and Its Relation to Dopaminergic Response in Parkinson's Disease

“…Thus the increase in number of STN cells with oscillatory beta activity might reflect the degree of nigrostriatal dopamine deficiency. The positive correlation between the magnitude of the levodopa response and the oscillatory activity we observed may be related to the increase in the magnitude of the levodopa response with progression of PD (Zappia et al 1997). This is consistent with the idea that abolishing the excessive beta activity by levodopa or DBS produces an improvement in parkinsonian symptoms.…”

The dopamine D2 receptor gene is a susceptibility locus for Parkinson's disease

“…They were part of a set of patients with PD who are seen on a regular basis at our Institute, and who were involved in a prospective pharmacologic study on short-and long-term effects of levodopa therapy. 17 Population control subjects consisted of healthy subjects of a similar age range as the cases and were drawn randomly during the same time period among an unselected sample of subjects that were part of a study on aging done in the region of Calabria, Italy, and frequency matched to the case patients for age (±10 yrs). All control subjects received a neurologic examination to exclude PD as well as a Mini Mental State Examination 18 to exclude demented subjects.…”

The role of the long-duration response to levodopa in Parkinson’s disease

“…In the early stages of PD, the improvement produced by the LDR is larger than the improvement produced by the SDR [6], and strategies to selectively induce the LDR may be adequate treatment of parkinsonism in these phases [7]. The LDR, however, also may be present in the more advanced stages of PD [5] and the maintenance over time of this response may preclude the development of a fluctuating motor response [8]. Moreover, the LDR is not associated with the long-term levodopa treatment complications such as dyskinesias and non-motor adverse effects that usually accompany the SDR.…”

“…Its presence ensures a stable and smooth drug efficacy [4] by fading the changes in motor disability associated with the SDR following the intake of single doses of levodopa [2,5]. In the early stages of PD, the improvement produced by the LDR is larger than the improvement produced by the SDR [6], and strategies to selectively induce the LDR may be adequate treatment of parkinsonism in these phases [7].…”