Clozapine improves dyskinesias in Parkinson disease

Durif, Franck; Debilly, Bérangère; Galitzky, Monique; Morand, Dominique; Viallet, François; Borg, Martin; Thobois, Stéphane; Broussolle, Emmanuel; Rascol, Olivier

doi:10.1212/01.wnl.0000110317.52453.6c

Cited by 203 publications

(95 citation statements)

References 36 publications

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“…Another, more selective, 5HT1A agonist, piclozotan, has also been developed, and is currently being tested in a multi-center, phase II trial in dyskinetic PD patients. There is also preliminary evidence that non-selective 5HT-2a, c receptor antagonists may have anti-dyskinetic effects Durif et al, 2004), although additional randomized trials are needed to confirm these observations (Katzenschlager et al, 2004). A summary of the key recent findings related to non-dopaminergic pharmacotherapies for Parkinson's disease is discussed in Box 3.…”

Section: Non-dopaminergic Therapiesmentioning

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: Non-dopaminergic Therapiesmentioning

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

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“…90 However, the use of clozapine in punders has not yet been reported. These promising hypotheses should be verified in future trials.…”

Section: Implications For Managementmentioning

confidence: 99%

Insights into pathophysiology of punding reveal possible treatment strategies

Fasano

Petrović²

2010

Mol Psychiatry

111

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Punding is a stereotyped behavior characterized by an intense fascination with a complex, excessive, nongoal oriented, repetitive activity. Men tend to repetitively tinker with technical equipment such as radio sets, clocks, watches and car engines, the parts of which may be analyzed, arranged, sorted and cataloged but rarely put back together. Women, in contrast, incessantly sort through their handbags, tidy continuously, brush their hair or polish their nails. Punders are normally aware of the inapposite and obtuse nature of the behavior; however, despite the consequent self-injury, they do not stop such behavior. The most common causes of punding are dopaminergic replacement therapy in patients affected by Parkinson's disease (PD) and cocaine and amphetamine use in addicts. The vast majority of information about punding comes from PD cases. A critical review of these cases shows that almost all afflicted patients (90%) were on treatment with drugs acting mainly on dopamine receptors D1 and D2, whereas only three cases were reported in association with selective D2 and D3 agonists. Epidemiological considerations and available data from animal models suggest that punding, drug-induced stereotypies, addiction and dyskinesias all share a common pathophysiological process. Punding may be related to plastic changes in the ventral and dorsal striatal structures, including the nucleus accumbens, and linked to psychomotor stimulation and reward mechanisms. Possible management guidelines are proposed.

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“…For example, the nonselective 5-HT 2A antagonists clozapine and quetiapine reduced dyskinesia-associated behaviors in the 6-OHDA-lesioned rodent and dyskinesia in the MPTP-lesioned primate (Oh et al, 2002;Visanji et al, 2006). In human studies, low-dose clozapine alleviated dyskinesia (Durif et al, 2004). The 5-HT 2A receptor inverse agonist pimavanserin (ACP-103) also reduced dyskinesia in MPTP-lesioned macaques (Vanover et al, 2008) and human PD subjects (Roberts, 2006).…”

Section: Introductionmentioning

confidence: 99%

Characterization of 3,4-Methylenedioxymethamphetamine (MDMA) EnantiomersIn Vitroand in the MPTP-Lesioned Primate:R-MDMA Reduces Severity of Dyskinesia, WhereasS-MDMA Extends Duration of ON-Time

Huot

Johnston²,

Lewis³

et al. 2011

J. Neurosci.

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1-methyl-4-phenyl-1,2,3,6tetrahydropyridine) administration. Motor disability, including parkinsonism and dyskinesia, and duration of antiparkinsonian benefit (ON-time) were evaluated. After the administration of R-MDMA (3 and 10 mg/kg), the severity of peak-dose dyskinesia was decreased (by 33 and 46%, respectively; p Ͻ 0.05); although total ON-time was unchanged (ϳ220 min), the duration of ON-time with disabling dyskinesia was decreased by 90 min when compared to L-DOPA alone (69% reduction; p Ͻ 0.05). S-MDMA (1 mg/kg) increased the total ON-time by 88 min compared to L-DOPA alone (34% increase; p Ͻ 0.05), though dyskinesia were exacerbated. These data suggest that racemic MDMA exerts simultaneous effects, reducing dyskinesia and extending ON-time, by 5-HT 2A antagonism and SERT-selective mixed monoamine uptake inhibition, which arise from its R and S enantiomers, respectively.

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Clozapine improves dyskinesias in Parkinson disease

Abstract: Clozapine is effective in the treatment of levodopa-induced dyskinesias in severe PD.

Cited by 203 publications

References 36 publications

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

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

Insights into pathophysiology of punding reveal possible treatment strategies

Characterization of 3,4-Methylenedioxymethamphetamine (MDMA) EnantiomersIn Vitroand in the MPTP-Lesioned Primate:R-MDMA Reduces Severity of Dyskinesia, WhereasS-MDMA Extends Duration of ON-Time

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