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Review Article
Emerging Nondopaminergic Medications for Parkinson’s Disease: Focusing on A2A Receptor Antagonists and GLP1 Receptor Agonists
Pei Shang, Matthew Baker, Samantha Banks, Sa-Ik Hong, Doo-Sup Choi
J Mov Disord. 2021;14(3):193-203.   Published online August 18, 2021
DOI: https://doi.org/10.14802/jmd.21035
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  • 5 Citations
AbstractAbstract PDF
Parkinson’s disease (PD) is a severe neurodegenerative disease characterized by classic motor features associated with the loss of dopaminergic neurons and appearance of Lewy bodies in the substantia nigra. Due to the complexity of PD, a definitive diagnosis in the early stages and effective management of symptoms in later stages are difficult to achieve in clinical practice. Previous research has shown that colocalization of A2A receptors (A2AR) and dopamine D2 receptors (D2R) may induce an antagonistic interaction between adenosine and dopamine. Clinical trials have found that the A2AR antagonist istradefylline decreases dyskinesia in PD and could be used as an adjuvant to levodopa treatment. Meanwhile, the incretin hormone glucagon-like peptide 1 (GLP1) mainly facilitates glucose homeostasis and insulin signaling. Preclinical experiments and clinical trials of GLP1 receptor (GLP1R) agonists show that they may be effective in alleviating neuroinflammation and sustaining cellular functions in the central nervous system of patients with PD. In this review, we summarize up-to-date findings on the usefulness of A2AR antagonists and GLP1R agonists in PD management. We explain the molecular mechanisms of these medications and their interactions with other neurotransmitter receptors. Furthermore, we discuss the efficacy and limitations of A2AR antagonists and GLP1R agonists in clinical practice.

Citations

Citations to this article as recorded by  
  • Adenosine receptors: Emerging non-opioids targets for pain medications
    Soo-Min Jung, Lee Peyton, Hesham Essa, Doo-Sup Choi
    Neurobiology of Pain.2022; 11: 100087.     CrossRef
  • A2A Adenosine Receptor Antagonists: Are Triazolotriazine and Purine Scaffolds Interchangeable?
    Andrea Spinaci, Catia Lambertucci, Michela Buccioni, Diego Dal Ben, Claudia Graiff, Maria Cristina Barbalace, Silvana Hrelia, Cristina Angeloni, Seyed Khosrow Tayebati, Massimo Ubaldi, Alessio Masi, Karl-Norbert Klotz, Rosaria Volpini, Gabriella Marucci
    Molecules.2022; 27(8): 2386.     CrossRef
  • Pathophysiological Role and Medicinal Chemistry of A2A Adenosine Receptor Antagonists in Alzheimer’s Disease
    Stefania Merighi, Pier Andrea Borea, Katia Varani, Fabrizio Vincenzi, Alessia Travagli, Manuela Nigro, Silvia Pasquini, R. Rama Suresh, Sung Won Kim, Nora D. Volkow, Kenneth A. Jacobson, Stefania Gessi
    Molecules.2022; 27(9): 2680.     CrossRef
  • Modulation of adenosine signaling reverses 3-nitropropionic acid-induced bradykinesia and memory impairment in adult zebrafish
    Melissa Talita Wiprich, Stefani Altenhofen, Darlan Gusso, Rafaela da Rosa Vasques, Rodrigo Zanandrea, Luiza Wilges Kist, Mauricio Reis Bogo, Carla Denise Bonan
    Progress in Neuro-Psychopharmacology and Biological Psychiatry.2022; 119: 110602.     CrossRef
  • A Focus on Astrocyte Contribution to Parkinson’s Disease Etiology
    Giselle Prunell, Silvia Olivera-Bravo
    Biomolecules.2022; 12(12): 1745.     CrossRef

JMD : Journal of Movement Disorders