Opiate Antagonists and Parkinson's Disease

Price, Paul; Baxter, R.C.; Parkes, J. D.; Marsden, C. D.

doi:10.1001/archneur.1979.00500460095021

Cited by 20 publications

(3 citation statements)

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“…Perhaps drugs acting on cannabinoid and opiate receptors will turn out to be more useful. For both there are conflicting reports showing agonist and antagonist molecules to have similar effects in the MPTP model and for disparate results in the clinic 203–217. However, this may be a question of understanding the complex pharmacology of these systems as recent publications have discussed (see for example Ref 218…”

Section: Are Nondopaminergic Approaches To Dyskinesia Control a Viablmentioning

confidence: 99%

Preventing and controlling dyskinesia in Parkinson's disease-A view of current knowledge and future opportunities

Jenner

2008

Mov. Disord.

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Dyskinesia affects approximately 30 to 40% of patients with Parkinson's disease but treatment options for the prevention of dyskinesia induction and for the suppression of established dyskinesia are limited. This situation is made more difficult by a poor understanding of the pathphysiology of the processes underlying both the priming for dyskinesia and the manifestations of involuntary movements. Loss of tonic stimulation of striatal dopamine receptors in PD and its replacement by pulsatile dopaminergic stimulation using short acting drugs has been proposed as leading to the abnormalities that cause dyskinesia induction. As a consequence, the concept of continuous dopaminergic stimulation (CDS) was introduced to explain why longer acting dopamine agonists do not produce the same intensity of dyskinesia. Key to these ideas has been the use of both 6-OHDA lesioned rodent models of PD and, in particular MPTP-treated primates. Comparison of the ability to induce dyskinesia of the same dopamine agonists given by pulsatile or continuous administration or more constant administration of Levodopa (L-dopa) has shown that constant drug delivery (CDD) dramatically reduces dyskinesia induction. Similar conclusions have been reached from clinical investigations in PD. Recent studies in MPTP-treated primates have also suggested that switching from pulsatile drug delivery to CDD can be utilized to inhibit dyskinesia expression. However, CDS does explain some important features of dyskinesia induction in PD but it may not apply to early PD when remaining dopaminergic neurones buffer against pulsatile stimulation. In addition, CDS may not apply when comparing between drug classes and it appears that it is CDD which is more important in regulating therapeutic efficacy. Recently, studies in MPTP-treated primates have suggested that a range of nondopaminerigic drugs might be useful in suppressing dyskinesia. These have included 5-HT-1A agonists and alpha-2 adrenergic antagonists and a variety of other molecular entities. Unfortunately, these findings are not always reproducible in the same models and do not translate into clinically useful effects. Preclinical studies have suggested a number of directions that might be utilized to prevent dyskinesia in PD. However, much of what is proposed is empirically-based and we still do not have a good understanding of why dyskinesia appears, why it persists or how to bring the movements under control. Certainly, the use of CDD can reduce dyskinesia intensity but other factors also influence its appearance and it is these that we need to study at the preclinical level if effective therapies are to be developed.

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Section: Are Nondopaminergic Approaches To Dyskinesia Control a Viablmentioning

confidence: 99%

Preventing and controlling dyskinesia in Parkinson's disease-A view of current knowledge and future opportunities

Jenner

2008

Mov. Disord.

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“…They pointed out that the doses used (100 mg per day for 10 days) may have been insufficient to block the appropriate striatal opiate receptors. Naloxone has also failed to improve the major signs of Parkinsonism (Price et al, 1979;Trabucchi et al, 1982) and dyskinesias (Price et al, 1979) however Trabucchi and colleagues found a significant improvement in patients with the "on-off phenomenon (probably not true "on-off' from their description of the stability of frequency and severity of fluctuations). Transitions from "on" to "off" became more gradual, the total "on" time increased and levodopainduced dyskinesias decreased.…”

Section: Peptidesmentioning

confidence: 99%

Treatment of Parkinson’s disease with agents other than Levodopa and Dopamine Agonists: controversies and new approaches

Lang

1984

Can. J. Neurol. Sci.

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Parkinson’s disease is associated with a variety of neurotransmitter disturbances which may be further altered by its treatment with dopamine agonists. Based on this information a wide range of pharmacological approaches have been used in search of newer treatment alternatives and in hopes of reducing complications of long-term levodopa use. This paper reviews the various therapies which have had some success in the management of Parkinson’s disease, other than levodopa and dopamine agonists. Special emphasis is placed on the many unresolved questions and controversies that exist in this area of neuropharmacology.

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“…One small‐scale, double‐blind, placebo‐controlled study in 6 patients, using the non‐subtype–selective opioid receptor antagonist, naloxone, showed a significant reduction in total daily dyskinesia and a reduction in rigidity 26. Case reports using naloxone have shown either a reduction27 or no effect 28. In all these studies, naloxone was administered as a bolus injection.…”

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confidence: 99%

Non‐subtype‐selective opioid receptor antagonism in treatment of levodopa‐induced motor complications in Parkinson's disease

et al. 2003

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Opioid peptide transmission is enhanced in the striatum of animal models and Parkinson's disease (PD) patients with levodopa-induced motor complications. Opioid receptor antagonists reduce levodopa-induced dyskinesia in primate models of PD; however, clinical trials to date have been inconclusive. A double-blind, placebo controlled, crossover design study in 14 patients with PD experiencing motor fluctuations was carried out, using the non-subtype-selective opioid receptor antagonist naloxone. Naloxone did not reduce levodopa-induced dyskinesia. The duration of action of levodopa was increased significantly by 17.5%. Non-subtype-selective opioid receptor antagonism may prove useful in the treatment of levodopa-related wearing-off in PD but not in dyskinesia.

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Opiate Antagonists and Parkinson's Disease

Cited by 20 publications

References 0 publications

Preventing and controlling dyskinesia in Parkinson's disease-A view of current knowledge and future opportunities

Preventing and controlling dyskinesia in Parkinson's disease-A view of current knowledge and future opportunities

Treatment of Parkinson’s disease with agents other than Levodopa and Dopamine Agonists: controversies and new approaches

Non‐subtype‐selective opioid receptor antagonism in treatment of levodopa‐induced motor complications in Parkinson's disease

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