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Critical Reviews™ in Neurobiology

ISSN for PRINT: 0892-0915

Institutional price:	$649.00
Issues per year:	4

Best Paper Award Selection - Editorial Board Site

2004, Volume16

194 pages

DOI: 10.1615/CritRevNeurobiol.v16.i12

Issue price - $252.00

Adenosine A_2A Receptor Antagonism and Neuroprotection: Mechanisms, Lights, and Shadows

Patrizia Popoli
Department of Drug Research and Evaluation, Istituto Superiore di Sanita, Roma, Italy

Luisa Minghetti
Department of Cell Biology and Neuroscience, Istituto Superiore di Sanita, Roma, Italy

Maria Teresa Tebano
Department of Drug Research and Evaluation, Istituto Superiore di Sanita, Roma, Italy

Annita Pintor
Department of Drug Research and Evaluation, Istituto Superiore di Sanita, Roma, Italy

Maria Rosaria Domenici
Department of Drug Research and Evaluation, Istituto Superiore di Sanita, Roma, Italy

Marino Massotti
Department of Drug Research and Evaluation, Istituto Superiore di Sanita, Roma, Italy

ABSTRACT

Adenosine A_2A receptor antagonists are regarded as potential neuroprotective drugs, although the mechanisms underlying their effects remain to be elucidated. In this review, quinolinic acid (QA)-induced striatal toxicity was used as a tool to investigate the mechanisms of the neuroprotective effects of A_2A receptor antagonists. After having examined the effects of selective A_2A receptor antagonists toward different mechanisms of QA toxicity, we conclude that (1) the effect elicited by A_2A receptor blockade on QA-induced glutamate outflow may be one of the mechanisms of the neuroprotective activity of A_2A receptor antagonists; (2) A_2A receptor antagonists have a potentially worsening influence on QA-dependent NMDA receptor activation; and (3) the ability of A_2A receptor antagonists to prevent QA-induced lipid peroxidation does not correlate with the neuroprotective effects.
These results suggest that A_2A receptor antagonists may have either potentially beneficial or detrimental influence in models of neurodegeneration that are mainly due to increased glutamate levels or enhanced sensitivity of NMDA receptors, respectively.