Effect of pergolide on endogenous and exogenous L-DOPA metabolism in the rat striatum: a microdialysis study

Dethy, Sophie; Laute, Marie-Aline; Luxen, André; Hildebrand, Jerzy; Goldman, Serge

doi:10.1007/bf01271541

Cited by 13 publications

(2 citation statements)

References 27 publications

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“…In previous reports, it has been demonstrated that pergolide inhibits endogenous DA release and exogenous L-dopa metabolism. 43 These observations suggest possibilities that pergolide increases endogenous dopamine level, and consequently quinoprotein formation is slightly increased after the L-dopa + pergolide treatment in our experiments.…”

Section: Discussionmentioning

confidence: 87%

Dopamine Agonist Pergolide Prevents Levodopa-Induced Quinoprotein Formation in Parkinsonian Striatum and Shows Quenching Effects on Dopamine-Semiquinone Generated in Vitro

Miyazaki

Asanuma²,

Díaz-Corrales

et al. 2005

Clinical Neuropharmacology

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The neurotoxicity of dopamine (DA) quinones that appears in dopaminergic neuron-specific oxidative stress has recently been shown to play a role in the pathogenesis and/or progression of Parkinson disease. To clarify the effects of a DA agonist, pergolide, on the levodopa-induced elevation of quinones, the authors examined striatal changes in quinoprotein using a hemi-parkinsonian mouse model. The level of striatal quinoprotein was significantly elevated specifically on the parkinsonian side, but not on the control side, after repeated levodopa administration. This levodopa-induced increase in striatal quinoprotein was almost completely suppressed by adjunctive administration with pergolide on the lesioned side. Furthermore, it was clarified that pergolide scavenged DA-semiquinones generated in vitro in a dose-dependent manner. These suppressive and quenching effects of pergolide against cytotoxic DA quinones may play a key role in its neuroprotective mechanism in the parkinsonian brain.

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Section: Discussionmentioning

confidence: 87%

Dopamine Agonist Pergolide Prevents Levodopa-Induced Quinoprotein Formation in Parkinsonian Striatum and Shows Quenching Effects on Dopamine-Semiquinone Generated in Vitro

Miyazaki

Asanuma²,

Díaz-Corrales

et al. 2005

Clinical Neuropharmacology

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“…2 ). No effects of dopamine agonists were found on the levels of the metabolite 5-HIAA ( 35 , 124 ). Additionally, it was suggested that D 2 receptor agonists modulate serotonin afferents presynaptically in the hippocampus ( 125 ) or the SN ( 126 ).…”

Section: Dopaminergic Treatment Effects On Endogenous Metabolites Levmentioning

confidence: 99%

Access to the CNS: Biomarker Strategies for Dopaminergic Treatments

et al. 2018

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Despite substantial research carried out over the last decades, it remains difficult to understand the wide range of pharmacological effects of dopaminergic agents. The dopaminergic system is involved in several neurological disorders, such as Parkinson’s disease and schizophrenia. This complex system features multiple pathways implicated in emotion and cognition, psychomotor functions and endocrine control through activation of G protein-coupled dopamine receptors. This review focuses on the system-wide effects of dopaminergic agents on the multiple biochemical and endocrine pathways, in particular the biomarkers (i.e., indicators of a pharmacological process) that reflect these effects. Dopaminergic treatments developed over the last decades were found to be associated with numerous biochemical pathways in the brain, including the norepinephrine and the kynurenine pathway. Additionally, they have shown to affect peripheral systems, for example the hypothalamus-pituitary-adrenal (HPA) axis. Dopaminergic agents thus have a complex and broad pharmacological profile, rendering drug development challenging. Considering the complex system-wide pharmacological profile of dopaminergic agents, this review underlines the needs for systems pharmacology studies that include: i) proteomics and metabolomics analysis; ii) longitudinal data evaluation and mathematical modeling; iii) pharmacokinetics-based interpretation of drug effects; iv) simultaneous biomarker evaluation in the brain, the cerebrospinal fluid (CSF) and plasma; and v) specific attention to condition-dependent (e.g., disease) pharmacology. Such approach is considered essential to increase our understanding of central nervous system (CNS) drug effects and substantially improve CNS drug development.

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Pergolide potentiates L-DOPA-induced dopamine release in rat striatum after lesioning with 6-hydroxydopamine

Dethy

Laute

Damhaut

et al. 1999

Journal of Neural Transmission

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We used intrastriatal microdialysis to study the effect of pergolide, a D1/D2 dopamine (DA) receptor agonist on biotransformation of exogenous L-DOPA in hemi-Parkinsonian rats. DA and metabolites were assayed by microbore liquid chromatography. Pergolide (50 micrograms/kg, i.p.) caused a 67% and 87% decrease in striatal EC levels of DA in intact and denervated striatum respectively. In intact striatum but not in denervated striatum, pergolide decreased EC levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) (53% and 42% decrease, respectively). L-DOPA (100 mg/kg, i.p.) produced significant increase in EC levels of DA, DOPAC and HVA in intact and denervated striatum with and without local perfusion of 10(-4) M pergolide. In denervated striatum, L-DOPA-induced DA increase was significantly higher in rats with pergolide. Our results suggest that, in an animal model of Parkinson's disease, pergolide in association with L-DOPA favors the restoration of striatal EC DA levels.

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Effect of pergolide on endogenous and exogenous L-DOPA metabolism in the rat striatum: a microdialysis study

Cited by 13 publications

References 27 publications

Dopamine Agonist Pergolide Prevents Levodopa-Induced Quinoprotein Formation in Parkinsonian Striatum and Shows Quenching Effects on Dopamine-Semiquinone Generated in Vitro

Dopamine Agonist Pergolide Prevents Levodopa-Induced Quinoprotein Formation in Parkinsonian Striatum and Shows Quenching Effects on Dopamine-Semiquinone Generated in Vitro

Access to the CNS: Biomarker Strategies for Dopaminergic Treatments

Pergolide potentiates L-DOPA-induced dopamine release in rat striatum after lesioning with 6-hydroxydopamine

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