Neuroprotection by pramipexole against dopamine- and levodopa-induced cytotoxicity

Zou, Linglong; Jankovic, Joseph; Rowe, Dominic B.; Xie, Wenjie; Appel, Stanley H.; Le, Weidong

doi:10.1016/s0024-3205(99)00062-4

Cited by 99 publications

(61 citation statements)

References 31 publications

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“…The present observations extend such reports in demonstrating similar affinities of numerous antiparkinson drugs at hD 2S versus hD 2L sites. Such information is important because 1) D 2S versus D 2L sites present differential patterns of post-translational processing, coupling, regulation, and localization; 2) D 2S autoreceptors modulate DA release and may contribute to neuroprotective properties of antiparkinson agents; and 3) postsynaptic D 2S and (predominant) hD 2L sites, perhaps via contrasting interactions with D 1 receptors, differentially control motor function (Zou et al, 1999;Usiello et al, 2000). hD 3 and hD 4 Receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Despite increasing interest in neuroprotective strategies, Parkinson's Disease is principally treated by administration of the dopamine (DA) precursor L-dihydroxyphenylalanine (L-DOPA) (Bezard et al, 2001). However, there is evidence, albeit contentious, that L-DOPA exacerbates damage to dopaminergic neurons (Zou et al, 1999). Furthermore, L-DOPA displays variable pharmacokinetics, elicits dyskinesias and autonomic side effects, poorly improves certain motor symptoms, is largely ineffective against cognitive and mood deficits, and loses efficacy upon prolonged administration (Bezard et al, 2001).…”

mentioning

confidence: 99%

“…In light of these observations, the management of Parkinson's Disease by drugs directly stimulating postsynaptic DA receptors is of interest (Jenner, 1995;Montastruc et al, 1999). Such dopaminergic agents possess neuroprotective properties, mediated by both dopaminergic (autoreceptor) and nondopaminergic mechanisms (Zou et al, 1999) and elicit less marked dyskinesia (Uitti and Ahlskog, 1996;Rascol et al, 2000). Furthermore, they may improve mood and cognitive function (Weddell and Weiser, 1995;Nagaraja and Jayashree, 2001).…”

mentioning

confidence: 99%

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Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. I. A Multivariate Analysis of the Binding Profiles of 14 Drugs at 21 Native and Cloned Human Receptor Subtypes

Millan

Maiofiss²,

Cussac³

et al. 2002

J Pharmacol Exp Ther

434

351

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Because little comparative information is available concerning receptor profiles of antiparkinson drugs, affinities of 14 agents were determined at diverse receptors implicated in the etiology and/or treatment of Parkinson's disease: human (h)D 1 , hD 2S , hD 2L , hD 3 , hD 4 , and hD 5 receptors; human 5-hydroxytryptamine (5-HT) 1A , h5-HT 1B , h5-HT 1D , h5-HT 2A , h5-HT 2B , and h5-HT 2C receptors; h␣ 1A -, h␣ 1B -, h␣ 1D -, h␣ 2A -, h␣ 2B -, h␣ 2C -, rat ␣ 2D -, h␤ 1 -, and h␤ 2 -adrenoceptors (ARs); and native histamine 1 receptors. A correlation matrix (294 pK i values) demonstrated substantial "covariance". Correspondingly, principal components analysis revealed that axis 1, which accounted for 76% variance, was associated with the majority of receptor types: drugs displaying overall high versus modest affinities migrated at opposite extremities. Axis 2 (7% of variance) differentiated drugs with high affinity for hD 4 and H 1 receptors versus h␣ 1 -AR subtypes. Five percent of variance was attributable to axis 3, which distinguished drugs with marked affinity for h␤ 1 -and h␤ 2 -ARs versus hD 5 and 5-HT 2A receptors. Hierarchical (cluster) analysis of global homology generated a dendrogram differentiating two major groups possessing low versus high affinity, respectively, for multiple serotonergic and hD 5 receptors. Within the first group, quinpirole, quinerolane, ropinirole, and pramipexole interacted principally with hD 2 , hD 3 , and hD 4 receptors, whereas piribedil and talipexole recognized dopaminergic receptors and h␣ 2 -ARs. Within the second group, lisuride and terguride manifested high affinities for all sites, with roxindole/bromocriptine, cabergoline/pergolide, and 6,7-dihydroxy-N,N-dimethyl-2-ammotetralin (TL99)/apomorphine comprising three additional subclusters of closely related ligands. In conclusion, an innovative multivariate analysis revealed marked heterogeneity in binding profiles of antiparkinson agents. Actions at sites other than hD 2 receptors likely participate in their (contrasting) functional profiles.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. I. A Multivariate Analysis of the Binding Profiles of 14 Drugs at 21 Native and Cloned Human Receptor Subtypes

Millan

Maiofiss²,

Cussac³

et al. 2002

J Pharmacol Exp Ther

434

351

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“…In contrast, other group has found dopamine receptors are not required to mediate the neuroprotective action of dopamine agonists [25]. For example, the inactive stereoisomers of PPX and apomorphine still have shown neuroprotective action in in vitro models despite their inability to activate dopamine receptors [26,27].…”

Section: Discussionmentioning

confidence: 94%

Pramipexole Protects Spinal Motor Neuron Death Against Glutamate-Induced Neurotoxicity

Kano

2011

J Neurol Res

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“…Furthermore, the degradation of levodopa generates many toxic metabolites that can cause oxidative stress in the neuron. Cultured dopaminergic neurons have undergone necrosis or apoptosis when exposed to levodopa, 12 suggesting that levodopa becomes toxic at a certain threshold. Another hypothesis is that levodopa preferentially exerts toxic effects in neurons previously damaged.…”

Section: Neuroprotectionmentioning

confidence: 99%

Neuroprotection in Parkinson Disease

Simpkins

Jankovic²

2003

Arch Intern Med

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Treatment of Parkinson disease has improved dramatically over the past quarter of a century and promising therapies are emerging. Although treatment with levodopa results in marked symptomatic improvement, mortality rates of the disease have remained relatively unchanged. Recent findings of abnormal protein folding, coupled with oxidative stress, provide scientific rationale for novel therapeutic strategies designed to slow disease progression. To be effective, these disease-modifying and neuroprotective therapies must be instituted early in the course of the disease and early diagnosis therefore is critical. Consequently, primary care physicians will play an increasingly important role in early institution of such neuroprotective strategies. This review is designed to highlight some of the recent advances in our understanding of the mechanisms of neurodegeneration and to draw attention to the importance of early recognition and implementation of the new therapeutic interventions.

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Neuroprotection by pramipexole against dopamine- and levodopa-induced cytotoxicity

Cited by 99 publications

References 31 publications

Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. I. A Multivariate Analysis of the Binding Profiles of 14 Drugs at 21 Native and Cloned Human Receptor Subtypes

Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. I. A Multivariate Analysis of the Binding Profiles of 14 Drugs at 21 Native and Cloned Human Receptor Subtypes

Pramipexole Protects Spinal Motor Neuron Death Against Glutamate-Induced Neurotoxicity

Neuroprotection in Parkinson Disease

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