The Long-Duration Action of Levodopa May Be Due to a Postsynaptic Effect

Barbato, Luca; Stocchi, Fabrizio; Monge, A.; Vacca, Laura; Ruggieri, Stefano; Nordera, Giampietro; Marsden, C. D.

doi:10.1097/00002826-199710000-00003

Cited by 53 publications

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“…7 In contrast, the long-duration response (LDR) lasts from days to weeks. It is evident clinically as a gradual improvement when levodopa is begun [8][9][10] and as a gradual worsening following cessation of therapy. 7,[10][11][12][13] The LDR is the largest component of symptomatic improvement during the first year of chronic levodopa therapy.…”

Section: Discussionmentioning

confidence: 99%

“…It is evident clinically as a gradual improvement when levodopa is begun [8][9][10] and as a gradual worsening following cessation of therapy. 7,[10][11][12][13] The LDR is the largest component of symptomatic improvement during the first year of chronic levodopa therapy. 7 Nutt et al 7 found that after 1 year of treatment, a 72-hour withdrawal of levodopa was insufficient to allow resolution of symptomatic benefit, as patients had not returned to baseline.…”

Section: Discussionmentioning

confidence: 99%

“…A slowly evolving postsynaptic pharmacodynamic change has been postulated. 10 Short-and long-duration responses have not been identified with bromocriptine therapy but its long halflife makes evaluation of such responses difficult. Tritium-labeled bromocriptine has a terminal serum halflife of approximately 48 hours.…”

Section: Discussionmentioning

confidence: 99%

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Time course of loss of clinical benefit following withdrawal of levodopa/carbidopa and bromocriptine in early Parkinson's disease

et al. 2000

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Time course of loss of clinical benefit following withdrawal of levodopa/carbidopa and bromocriptine in early Parkinson's disease

et al. 2000

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“…The observations that the LDR also occurs with the dopamine agonists ropinirole [15] and apomorphine [16] may indeed suggest that the LDR could be postsynaptic in origin. Nevertheless, further studies are needed to confirm this important issue.…”

Section: Pharmacological Mechanismsmentioning

confidence: 97%

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

Zappia

2010

J Neurol

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The long-duration response (LDR) to levodopa is an important component of the therapeutic response to the drug in Parkinson's disease (PD). Some characteristics are peculiar: it is independent from peripheral pharmacokinetics of levodopa, but it is dependent on the intervals between doses and on the size of each dose. Once the LDR fully develops, it is stable and maximal. After stopping treatment, the decay rate is inversely related to the severity of PD; when the LDR decreases over time, the patients present a fluctuating motor response. Therapeutic strategies based on the development and maintenance of the LDR should be sought to maximize the clinical benefit induced by levodopa and to avoid the appearance of motor complications.

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“…Strong support for the involvement of postsynaptic mechanisms comes from the slow decay of the LDR on withdrawing dopamine agonist treatment in patients with de novo PD. For example, the time taken for motor symptoms to deteriorate back to baseline after stopping treatment with ropinirole (9–21 mg daily) was 6.2 ± 1.7 days [34] and 9.0 ± 1.9 days with the short-acting agonist lisuride [35]. Interestingly, similar studies in de novo PD patients with the very long-acting dopamine agonist cabergoline showed a shorter LDR compared to short-acting lisuride.…”

Section: Postsynaptic Mechanisms In Wearing-offmentioning

confidence: 99%

When Do Levodopa Motor Fluctuations First Appear in Parkinson’s Disease?

2010

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Although levodopa provides therapeutic benefit over the entire course of Parkinson’s disease, most patients eventually notice a decline in the duration of benefit from each dose, a phenomenon termed ‘wearing-off’ or ‘end of dose’ deterioration. This is an important indicator that the patient is entering a more complex phase of the disease. Wearing-off has been classically associated with the later stages of Parkinson’s disease, but it is becoming apparent that patients with early disease, presenting as well controlled, may already be experiencing fluctuations in their response to levodopa. However, neither the pathophysiology nor the clinical relevance of the early emergence of wearing-off has been properly explored. We now review the preclinical and clinical evidence that suggests that even patients who are apparently still in the honeymoon phase of drug treatment may have early fluctuations in their motor response to dopaminergic therapy. It is important that early wearing-off is recognized as it has important consequences for the long-term outcome and for the medication regimens to be used.

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The Long-Duration Action of Levodopa May Be Due to a Postsynaptic Effect

Cited by 53 publications

References 0 publications

Time course of loss of clinical benefit following withdrawal of levodopa/carbidopa and bromocriptine in early Parkinson's disease

Time course of loss of clinical benefit following withdrawal of levodopa/carbidopa and bromocriptine in early Parkinson's disease

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

When Do Levodopa Motor Fluctuations First Appear in Parkinson’s Disease?

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