Similarities between Neurologic Effects of L-Dopa and of Apomorphine

Cotzias, George C.; Papavasiliou, Paul S.; Fehling, Clas; Kaufman, Barry; Mena, I

doi:10.1056/nejm197001012820107

Cited by 269 publications

(87 citation statements)

References 8 publications

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“…Clinical improvements start within 20 min of administration when the drug appears in the cerebrospinal fluid. Double-blind clinical trials have shown the effectiveness of subcutaneously injected apomorphine in improving PD motor symptoms (Cotzias et al, 1970;Dewey et al, 2001). Despite these benefits, the longterm use of subcutaneous apomorphine infusions in the United Kingdom has been associated with significant technical difficulties and cutaneous adverse effects (Hughes et al, 1993).…”

Section: Dopamine Replacement Therapymentioning

confidence: 99%

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Smith

Wichmann

Factor

et al. 2011

Neuropsychopharmacol

194

137

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The demonstration that dopamine loss is the key pathological feature of Parkinson's disease (PD), and the subsequent introduction of levodopa have revolutionalized the field of PD therapeutics. This review will discuss the significant progress that has been made in the development of new pharmacological and surgical tools to treat PD motor symptoms since this major breakthrough in the 1960s. However, we will also highlight some of the challenges the field of PD therapeutics has been struggling with during the past decades. The lack of neuroprotective therapies and the limited treatment strategies for the nonmotor symptoms of the disease (ie, cognitive impairments, autonomic dysfunctions, psychiatric disorders, etc.) are among the most pressing issues to be addressed in the years to come. It appears that the combination of early PD nonmotor symptoms with imaging of the nigrostriatal dopaminergic system offers a promising path toward the identification of PD biomarkers, which, once characterized, will set the stage for efficient use of neuroprotective agents that could slow down and alter the course of the disease.

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Section: Dopamine Replacement Therapymentioning

confidence: 99%

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Smith

Wichmann

Factor

et al. 2011

Neuropsychopharmacol

194

137

View full text Add to dashboard Cite

show abstract

“…3 The product was not developed further at that time as a therapy for PD, possibly due to both the emergence of oral dopaminergic drugs and the reluctance of neurologists to use an injectable formulation, but also due to its emetic properties. Subsequently, as a result of new pump technology in the field of diabetes and the availability of the anti-emetic domperidone, a clinical trial of apomorphine infusion for the management of Parkinsonian ON-OFF oscillations was undertaken by Stibe and colleagues.…”

Section: Andrew Leesmentioning

confidence: 99%

Twenty Years of Apomorphine Therapy – How Does it Compare with Levodopa?

Lees¹,

Isaacson²

2015

European Neurological Review

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Apomorphine administered subcutaneously has provided clinicians with an effective option for the rapid resolution of the symptoms of Parkinson's disease (PD) for over a quarter of a century. It is available for use either as an intermittent injection or a continuous infusion, depending on the severity of the patient's symptoms. This satellite symposium, held during the 18th International Congress of Parkinson's Disease and Movement Disorders in Stockholm, Sweden, from 8-12 June 2014, and chaired by Professor Andrew Lees, set out to review the extensive clinical experience of subcutaneous apomorphine in the management of PD accumulated over the past 25 years. It also aimed to explore why it continues to play such a valuable therapeutic role in this setting. The presenters highlighted key clinical data demonstrating why apomorphine is an effective choice for the management of both motor and non-motor symptoms in PD. Results from the limited number of comparative studies of apomorphine continuous infusion with other therapies for complex PD suggest that it has a robust motor effect, resulting in a reduction of OFF periods comparable to that achieved with more invasive options such as intrajejunal levodopa infusion or deep brain stimulation. In a large European study, apomorphine infusion has been shown to provide similar improvements in health-related quality of life to intrajejunal levodopa infusion but with a superior side-effect profile. In addition, apomorphine infusion has demonstrated beneficial non-motor effects in PD patients and reports suggest it is associated with low rates of impulse control disorders (ICDs). The motor fluctuations that occur over time in PD patients treated with oral levodopa present a management challenge as the disease progresses. Many PD patients experience these OFF periods despite optimised oral therapy and the use of multiple medications. They are due to both end-of-dose wearing OFF and delayed time to ON (TTO). A prolonged TTO is common in PD patients who have gastroparesis (delayed gastric emptying) whereby the levodopa dose is delayed exiting the stomach and is slow in reaching its site of absorption in the small intestine. Alternative non-oral formulations that avoid the gastrointestinal route, such as subcutaneous apomorphine intermittent injection, have therefore been investigated for the relief of motor fluctuations in this setting. Interim results from the ongoing Apokyn for Motor IMProvement of Morning AKinesia Trial (AM IMPAKT) study have shown that subcutaneous apomorphine injection is a valuable treatment option in PD patients with morning akinesia. This is due to a delayed onset of levodopa dose as it produces a rapid and reliable TTO, with 95 % of patients achieving at least a 20-minute reduction in TTO and an average reduction of 40 minutes. Patients also experienced improvements in Unified Parkinson's Disease Rating Scale (UPDRS) motor score and Hoehn and Yahr stage, as well as measures of quality of life and global impression of severity.

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“…Apomorphine was the first dopamine receptor agonist used to treat Parkinson's disease over 60 years ago (Schwab et al, 1951;Cotzias et al, 1970). It is an a short-term agonist dopamine that direct acts on D1 and D2 receptors (Kempster et al, 1990;Colosimo et al, 1996), with clinical antiparkinsonian action very powerful, equivalent to the LD, both qualitatively and quantitatively.…”

Section: Apomorphinementioning

confidence: 99%