Document Detail


Adenosine A(2A)-Receptor Antagonism and Pathophysiology of Parkinson's Disease and Drug-Induced Movement Disorders.
MedLine Citation:
PMID:  22134373     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Parkinson's disease and drug-induced movement disorders (DIMDs) have commonalities in etiology based on impaired dopamine-based neurotransmission. Adenosine A(2A)-receptor antagonism may provide a new mechanism through which these disorders can be managed. In the motor circuit, tonic output from the globus pallidus and substantia nigra regulates movement via opposing excitatory and inhibitory inputs to the cerebral cortex through the direct and indirect pathways. Increased activity of the direct pathway increases movement via an inhibitory effect on thalamocortical projection neurons; increased activity of the indirect pathway has the opposite effect. Regulation of these pathways is mediated primarily by reciprocal inhibitory interactions between dopamine and adenosine receptors on neurons of these pathways. Adenosine A(2A) receptors are colocalized with dopamine D(2) receptors on the indirect pathway neurons, with A(2A) activation opposing the effect of D(2) activation. The A(2A) receptors' role in the pathophysiology of Parkinson's disease and DIMDs is evidenced by the upregulation of A(2A) receptors in patients with Parkinson's disease and patients receiving long-term administration of dopamine blockers. Further, A(2A)-receptor antagonists are effective in reversing parkinsonian motor deficits and extrapyramidal symptoms in animal models of Parkinson's disease and DIMDs. Understanding the role of A(2A)-receptor antagonism in the pathophysiology of Parkinson's disease and DIMD has therapeutic implications.
Authors:
Jaime Kulisevsky; Michael Poyurovsky
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-30
Journal Detail:
Title:  European neurology     Volume:  67     ISSN:  1421-9913     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-12-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0150760     Medline TA:  Eur Neurol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  4-11     Citation Subset:  -    
Copyright Information:
Copyright © 2011 S. Karger AG, Basel.
Affiliation:
Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Institute of Biomedical Research (IIB-Sant Pau) Barcelona, Barcelona, Spain.
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