Can adenosine A2A receptor antagonists be used to treat cognitive impairment, depression or excessive sleepiness in Parkinson's disease?

Jenner, Peter; Mori, Akihisa; Kanda, Tomoyuki

doi:10.1016/j.parkreldis.2020.09.022

Cited by 26 publications

(24 citation statements)

References 106 publications

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“…A recent openlabel, small-scale clinical study demonstrated the effectiveness of istradefylline on daytime sleepiness in patients with PD [11]. Furthermore, several studies have shown that istradefylline has positive effects on depression and anxiety in animal models (reviewed in [22]) and in patients with PD [10], However, our study showed no significant effects of istradefylline on these NMSs. This discrepancy may be explained in terms of anatomical features and the pathological changes during the course of PD.…”

Section: Possible Therapeutic Mechanisms Of Istradefylline On Nmsscontrasting

confidence: 71%

Influence of istradefylline on non-motor symptoms of Parkinson's disease: A subanalysis of a 1-year observational study in Japan (J-FIRST)

Shimo

Maeda

Chiu

et al. 2021

Parkinsonism & Related Disorders

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The non-motor symptoms (NMSs) of Parkinson's disease (PD) significantly impact the patient's health-related quality of life. This subanalysis of the J-FIRST study evaluated the effect of istradefylline, a selective adenosine A 2A receptor antagonist, on NMSs in istradefylline-naïve Japanese patients with PD. Methods: Patients with PD and ≥1 NMS and 'wearing-off' with their current antiparkinsonian treatment were observed for up to 52 weeks. The effect of istradefylline on NMSs was measured in terms of changes in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 1 total, individual subitems scores and the 8 item PD questionnaire (PDQ-8) estimated by the marginal structural model. Results: Overall, 732 patients were istradefylline-naïve prior to the study, of whom 171 were treated with istradefylline for ≥8 weeks during the observation period (istradefylline-treated patients). At baseline, istradefylline-treated patients were more likely to have a dyskinesia (49.7% vs 40.8%) and received a significantly higher daily dose of levodopa (462.8 mg vs 413.0 mg) than those who did not receive istradefylline (n = 561). MDS-UPDRS Part 1 total score at the end of the 52-week observational period slightly increased in patients who received istradefylline and those who did not (0.49 ± 0.41 vs 0.07 ± 0.20; P = 0.36). There were no statistically significant differences between the two groups of patients in terms of changes in the MDS-UPDRS Part 1 total score or any sub-items, or in the PDQ-8 total score. Conclusion: NMSs remained generally controlled in istradefylline-treated Japanese patients with PD who exhibited wearing-off with their current antiparkinsonian treatment. Istradefylline could be a feasible treatment option for patients with advanced PD, without worsening existing NMSs.

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Section: Possible Therapeutic Mechanisms Of Istradefylline On Nmsscontrasting

confidence: 71%

Influence of istradefylline on non-motor symptoms of Parkinson's disease: A subanalysis of a 1-year observational study in Japan (J-FIRST)

Shimo

Maeda

Chiu

et al. 2021

Parkinsonism & Related Disorders

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“…The data collected thus far therefore suggest that A 2A ARs antagonists may be useful in the treatment of motor and non-motor symptoms, including depression and sleep disorders. Such compounds may also have positive effects on the cognitive deficits associated with the disease, particularly on short-term memory [141,142].…”

Section: Attention-deficit Hyperactivity Disorder (Adhd)mentioning

confidence: 99%

Adenosine Receptors in Neuropsychiatric Disorders: Fine Regulators of Neurotransmission and Potential Therapeutic Targets

Pasquini

Contri

Merighi

et al. 2022

IJMS

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Adenosine exerts an important role in the modulation of central nervous system (CNS) activity. Through the interaction with four G-protein coupled receptor (GPCR) subtypes, adenosine subtly regulates neurotransmission, interfering with the dopaminergic, glutamatergic, noradrenergic, serotoninergic, and endocannabinoid systems. The inhibitory and facilitating actions of adenosine on neurotransmission are mainly mediated by A1 and A2A adenosine receptors (ARs), respectively. Given their role in the CNS, ARs are promising therapeutic targets for neuropsychiatric disorders where altered neurotransmission represents the most likely etiological hypothesis. Activating or blocking ARs with specific pharmacological agents could therefore restore the balance of altered neurotransmitter systems, providing the rationale for the potential treatment of these highly debilitating conditions. In this review, we summarize and discuss the most relevant studies concerning AR modulation in psychotic and mood disorders such as schizophrenia, bipolar disorders, depression, and anxiety, as well as neurodevelopment disorders such as autism spectrum disorder (ASD), fragile X syndrome (FXS), attention-deficit hyperactivity disorder (ADHD), and neuropsychiatric aspects of neurodegenerative disorders.

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“…Auch bei Parkinson-Patienten wird für A 2A Rezeptorantagonisten eine Reduktion der Tagesschläfrigkeit nach der Epworth Sleepiness Scale (ESS) berichtet, ohne dass der Nachtschlaf beeinträchtigt wird, wie anhand der Parkinson Disease Sleep Scale (PDSS) bestätigt wurde 58 59 . Große, doppelblinde und placebokontrollierte Studien zu diesem Parameter stehen aus 11 .…”

Section: Evidenz Von a 2a Rezeptorantagonisten Bei Mo...unclassified

Adenosin A2A Rezeptorantagonisten als Therapieoption beim idiopathischen Parkinson-Syndrom?

Jost

Tönges

2022

Fortschr Neurol Psychiatr

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ZusammenfassungBeim Parkinson-Syndrom wurde sich lange Zeit auf die motorischen Symptome und die Therapie mit dopaminergen Substanzen fokussiert. In den letzten Jahren gewannen die nicht-motorischen Symptome immer mehr Bedeutung, da sie früh im Krankheitsverlauf auftreten und die Lebensqualität erheblich einschränken. Dadurch wurde aber auch die Notwendigkeit einer Behandlung nicht nur des dopaminergen Defizits offensichtlich. Als weitere therapeutische Option wurden die Adenosin A2A Rezeptorantagonisten entwickelt, da Adenosin A2A Rezeptorantagonisten nicht-dopaminerg und selektiv in den Basalganglien lokalisiert sind. Somit besteht die Möglichkeit striato-thalamo-kortikalen Schleifen zusätzlich zu modulieren. Bereits 2013 wurde ein Adenosin A2A Rezeptorantagonist in Japan und in 2019 in den USA als Add-on zu L-DOPA zugelassen. Mit einer Zulassung in Europa wird in naher Zukunft gerechnet. In dieser Übersicht möchten wir die theoretischen Grundlagen dieses Therapieansatzes darstellen und die aktuellen Daten zur Wirksamkeit und dem therapeutischen Einsatz referieren.

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Can adenosine A2A receptor antagonists be used to treat cognitive impairment, depression or excessive sleepiness in Parkinson's disease?

Cited by 26 publications

References 106 publications

Influence of istradefylline on non-motor symptoms of Parkinson's disease: A subanalysis of a 1-year observational study in Japan (J-FIRST)

Influence of istradefylline on non-motor symptoms of Parkinson's disease: A subanalysis of a 1-year observational study in Japan (J-FIRST)

Adenosine Receptors in Neuropsychiatric Disorders: Fine Regulators of Neurotransmission and Potential Therapeutic Targets

Adenosin A2A Rezeptorantagonisten als Therapieoption beim idiopathischen Parkinson-Syndrom?

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