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Therapeutic potential of adenosine A(2A) receptor antagonists in Parkinson's disease.
Pharmacol Ther. 2005 Mar; 105(3):267-310.P&T

Abstract

In the pursuit of improved treatments for Parkinson's disease (PD), the adenosine A(2A) receptor has emerged as an attractive nondopaminergic target. Based on the compelling behavioral pharmacology and selective basal ganglia expression of this G-protein-coupled receptor, its antagonists are now crossing the threshold of clinical development as adjunctive symptomatic treatment for relatively advanced PD. The antiparkinsonian potential of A(2A) antagonism has been boosted further by recent preclinical evidence that A(2A) antagonists might favorably alter the course as well as the symptoms of the disease. Convergent epidemiological and laboratory data have suggested that A(2A) blockade may confer neuroprotection against the underlying dopaminergic neuron degeneration. In addition, rodent and nonhuman primate studies have raised the possibility that A(2A) receptor activation contributes to the pathophysiology of dyskinesias-problematic motor complications of standard PD therapy--and that A(2A) antagonism might help prevent them. Realistically, despite being targeted to basal ganglia pathophysiology, A(2A) antagonists may be expected to have other beneficial and adverse effects elsewhere in the central nervous system (e.g., on mood and sleep) and in the periphery (e.g., on immune and inflammatory processes). The thoughtful design of new clinical trials of A(2A) antagonists should take into consideration these counterbalancing hopes and concerns and may do well to shift toward a broader set of disease-modifying as well as symptomatic indications in early PD.

Authors+Show Affiliations

Xu K
MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA 02129, USA.
Bastia E
No affiliation info available
Schwarzschild M
No affiliation info available

MeSH

Adenosine A2 Receptor AntagonistsAnimalsBrainCaffeineCentral Nervous System StimulantsClinical Trials as TopicHumansParkinson DiseasePurinesReceptors, Adenosine A2

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

15737407

Citation

Xu, Kui, et al. "Therapeutic Potential of Adenosine A(2A) Receptor Antagonists in Parkinson's Disease." Pharmacology & Therapeutics, vol. 105, no. 3, 2005, pp. 267-310.
Xu K, Bastia E, Schwarzschild M. Therapeutic potential of adenosine A(2A) receptor antagonists in Parkinson's disease. Pharmacol Ther. 2005;105(3):267-310.
Xu, K., Bastia, E., & Schwarzschild, M. (2005). Therapeutic potential of adenosine A(2A) receptor antagonists in Parkinson's disease. Pharmacology & Therapeutics, 105(3), 267-310.
Xu K, Bastia E, Schwarzschild M. Therapeutic Potential of Adenosine A(2A) Receptor Antagonists in Parkinson's Disease. Pharmacol Ther. 2005;105(3):267-310. PubMed PMID: 15737407.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic potential of adenosine A(2A) receptor antagonists in Parkinson's disease. AU - Xu,Kui, AU - Bastia,Elena, AU - Schwarzschild,Michael, Y1 - 2004/12/21/ PY - 2004/10/14/received PY - 2004/10/14/accepted PY - 2005/3/2/pubmed PY - 2005/6/23/medline PY - 2005/3/2/entrez SP - 267 EP - 310 JF - Pharmacology & therapeutics JO - Pharmacol Ther VL - 105 IS - 3 N2 - In the pursuit of improved treatments for Parkinson's disease (PD), the adenosine A(2A) receptor has emerged as an attractive nondopaminergic target. Based on the compelling behavioral pharmacology and selective basal ganglia expression of this G-protein-coupled receptor, its antagonists are now crossing the threshold of clinical development as adjunctive symptomatic treatment for relatively advanced PD. The antiparkinsonian potential of A(2A) antagonism has been boosted further by recent preclinical evidence that A(2A) antagonists might favorably alter the course as well as the symptoms of the disease. Convergent epidemiological and laboratory data have suggested that A(2A) blockade may confer neuroprotection against the underlying dopaminergic neuron degeneration. In addition, rodent and nonhuman primate studies have raised the possibility that A(2A) receptor activation contributes to the pathophysiology of dyskinesias-problematic motor complications of standard PD therapy--and that A(2A) antagonism might help prevent them. Realistically, despite being targeted to basal ganglia pathophysiology, A(2A) antagonists may be expected to have other beneficial and adverse effects elsewhere in the central nervous system (e.g., on mood and sleep) and in the periphery (e.g., on immune and inflammatory processes). The thoughtful design of new clinical trials of A(2A) antagonists should take into consideration these counterbalancing hopes and concerns and may do well to shift toward a broader set of disease-modifying as well as symptomatic indications in early PD. SN - 0163-7258 UR - https://www.unboundmedicine.com/medline/citation/15737407/Therapeutic_potential_of_adenosine_A_2A__receptor_antagonists_in_Parkinson's_disease_ DB - PRIME DP - Unbound Medicine ER -