期刊
PHARMACOLOGY & THERAPEUTICS
卷 132, 期 3, 页码 280-299出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2011.07.004
关键词
Basal ganglia; Receptor heteromer; Heteromer-selective antagonist; Neuroprotection; Postsynaptic heteromer; Presynaptic heteromer
资金
- Spanish Ministry of Science and Innovation [SAF2008-03229-E, SAF2009-07276, SAF2008-03118-E]
- German Federal Ministry for Education and Research (BMBF) Germany [01EW0911]
- Italian Ministry of Health (MTA, AP) [RC2008MinSal/Era-NET]
- National Institute in Drug Abuse
Several selective antagonists for adenosine A(2A) receptors (A(2A)R) are currently under evaluation in clinical trials (phases I to III) to treat Parkinson's disease, and they will probably soon reach the market. The usefulness of these antagonists has been deduced from studies demonstrating functional interactions between dopamine D-2 and adenosine A(2A) receptors in the basal ganglia. At present it is believed that A(2A)R antagonists can be used in combination with the dopamine precursor L-DOPA to minimize the motor symptoms of Parkinson's patients. However, a considerable body of data indicates that in addition to ameliorating motor symptoms, adenosine A(2A)R antagonists may also prevent neurodegeneration. Despite these promising indications, one further issue must be considered in order to develop fully optimized antiparkinsonian drug therapy, namely the existence of (hetero)dimers/oligomers of G protein-coupled receptors, a topic that is currently the focus of intense debate within the scientific community. Dopamine D-2 receptors (D(2)Rs) expressed in the striatum are known to form heteromers with A(2A) adenosine receptors. Thus, the development of heteromer-specific A(2A) receptor antagonists represents a promising strategy for the identification of more selective and safer drugs. (C) 2011 Elsevier Inc. All rights reserved.
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