Cabergoline: A Promising Agent for the Treatment of Parkinson's Disease

Grondin, Richard; Bédard, Paul J.

doi:10.1111/j.1527-3458.1996.tb00298.x

Cited by 3 publications

(1 citation statement)

References 54 publications

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“…Cabergoline represents a useful tool for the treatment of PD, because the stimulation of postsynaptic dopamine receptors by this dopamine receptor agonist increases locomotor activity of normal animals and reverses akinesia in MPTP monkeys 45, 59–62. Combined with levodopa therapy, in PD patients, cabergoline (2–10 mg/day) significantly decreases the number of off hours compared to placebo 60.…”

Section: Discussionmentioning

confidence: 99%

Chronic treatment with small doses of cabergoline prevents dopa‐induced dyskinesias in parkinsonian monkeys

et al. 2003

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Levodopa continues to be the most effective agent for the symptomatic treatment of Parkinson's disease (PD). But over time, initial benefits decline in efficacy because of a rise in adverse effects such as dyskinesias. The pathophysiology of levodopa-induced dyskinesias (LID) is not completely understood, but it appears to result from deficient regulation by dopamine of corticostriatal glutamatergic inputs leading to a cascade of neurochemical changes in the striatum and the output pathways. In the present study, we examined if the addition of small doses of cabergoline (a long-acting D(2) receptor agonist) to levodopa could prevent LID. The major hypothesis is that sustained activation of postsynaptic D(2) receptors on medium spiny neurons even by small doses of cabergoline could prevent or reduce LID. The minor hypothesis, and the more controversial of the two, is that the long-acting stimulation by small doses of cabergoline could diminish the release of glutamate by the corticostriatal pathway and prevent LID. Eight MPTP-treated monkeys with a long-standing and stable parkinsonian syndrome and having never received dopaminergic agents were used. Two groups of four were treated for 1 month with levodopa/benserazide administered orally (100 mg/25 mg). The second group received in addition a threshold dose of cabergoline (dose ranging from 0.015 to 0.035 mg/kg, SC). During the treatment, we observed LID in the levodopa group but not in the group receiving levodopa+cabergoline. Furthermore, the combination produced a comparable antiparkinsonian effect in terms of quality but prolonged the duration (by 1 to 2 hours) and increased the locomotion (mean for 2 weeks congruent with 104%). Our data suggest that a small dose of a long-acting D(2) agonist combined with high doses of levodopa could be preventive of LID in patients with PD and could be an alternative to using antiglutamatergic agents for this purpose.

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Section: Discussionmentioning

confidence: 99%

Chronic treatment with small doses of cabergoline prevents dopa‐induced dyskinesias in parkinsonian monkeys

et al. 2003

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Rationale for Use of Dopamine Agonists in Parkinson's Disease: Review of Ergot Derivatives

Blanchet

1999

Can. J. Neurol. Sci.

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The role and optimal timing of introduction of dopamine agonists in the symptomatic treatment of Parkinson's disease (PD) are still unsettled. Reevaluation of these issues is required in light of new experimental data published on crucial therapeutic issues revolving around the mechanisms of induction of motor response complications and cell death. In spite of suggestive animal evidence that levodopa may be harmful to compromised dopamine neurons in vivo, 1-2 there is no direct proof yet that levodopa results in irreversible dysfunction of the basal ganglia and catecholaminergic cell death in humans.3 Nonetheless, strategies to reduce (adjunct agonist therapy) or even replace (agonist monotherapy de novo) levodopa early in the disease have been explored for many years in an attempt to reduce long-term adverse effects. The advantages of direct dopamine agonists in PD include the lack of competition with dietary amino acids for absorption and absence of necessary enzymatic metabolic steps, leading to more reliable and consistent effects, a long duration of efficacy, greater potency, potential alternative modes of delivery, a reduced incidence of early motor response complications and possible neuroprotective properties. The clinical efficacy of the ergot derivatives is briefly reviewed to provide useful information for comparing their effects with newer dopamine agonists. ABSTRACT: While dopamine agonists are still traditionally used as adjunct medications to improve performance and smooth out motor response complications in advanced levodopa-treated Parkinson's disease, they are increasingly used in monotherapy or early in combination with levodopa particularly in patients under 65 years of age. Long-term studies using bromocriptine showed efficacy in lowering the cumulative levodopa dose and reducing the early incidence of levodopa-related motor response complications. New dopamine agonists have recently shown efficacy as adjunct medications in short-term trials. While we now have more options to fit our individual patients' needs and tolerance, it is important to view the new agonists in the light of the results obtained with ergot derivatives. In this article, the rationale for use and efficacy profile of the ergolines are briefly reviewed. Can. PHARMACOLOGICAL PROPERTIES

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Sustained Cabergoline Treatment Reverses Levodopa-Induced Dyskinesias in Parkinsonian Monkeys

Tahar

Grégoire

Bangassoro

et al. 2000

Clinical Neuropharmacology

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The pathophysiology of L-Dopa-induced dyskinesias (LID), a common problem after long-term use of L-dopa in the treatment of Parkinson's disease (PD), is not completely understood. Oscillations in L-Dopa concentrations in the brain are believed to be responsible, at least in part, for their pathogenesis. This study was aimed at verifying whether chronic administration of cabergoline, a long-acting dopamine D2-like receptor agonist, can reverse established LID. Four MPTP-treated cynomolgus monkeys with long-standing and stable parkinsonian syndrome and reproducible dyskinesias to L-Dopa, were used in this study. We compared the antiparkinsonian and dyskinetic responses of L-Dopa methyl ester (62.5 mg and 125 mg), given with benserazide (50 mg) (L-Dopa/benserazide), administered before and after a 6-week period during which the animals were treated only by daily administration of cabergoline (doses ranging from 0.125 to 0.185 mg/kg, subcutaneous). During cabergoline treatment, the monkeys initially showed marked dyskinesias, which were reduced significantly after 4 weeks of treatment. However, there was no tolerance to its antiparkinsonian effect. L-Dopa/benserazide given 4 days after cabergoline withdrawal produced a significant antiparkinsonian effect, but dyskinesias were dramatically reduced compared to what had been seen before chronic cabergoline treatment. The duration of the L-Dopa response was not increased after chronic administration of cabergoline. Our data suggest that sustained dopamine D2 receptor stimulation could be of value when trying to reduce or to reverse LID in patients with fluctuating advanced PD.

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Cabergoline: A Promising Agent for the Treatment of Parkinson's Disease

Cited by 3 publications

References 54 publications

Chronic treatment with small doses of cabergoline prevents dopa‐induced dyskinesias in parkinsonian monkeys

Chronic treatment with small doses of cabergoline prevents dopa‐induced dyskinesias in parkinsonian monkeys

Rationale for Use of Dopamine Agonists in Parkinson's Disease: Review of Ergot Derivatives

Sustained Cabergoline Treatment Reverses Levodopa-Induced Dyskinesias in Parkinsonian Monkeys

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