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Unexpected neuroprotection observed with the adenosine A 2A receptor agonist CGS 21680
Author(s) -
Sheardown Malcolm J.,
Knutsen Lars J.S.
Publication year - 1996
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(19960901)39:1<108::aid-ddr8>3.0.co;2-j
Subject(s) - cgs 21680 , agonist , adenosine a2a receptor , adenosine , chemistry , medicine , endocrinology , receptor , neuroprotection , adenosine receptor , pharmacology , biology , biochemistry
The selective adenosine A 2A receptor agonists 2‐[ p ‐(2‐carboxethyl)phenylethylaminol‐5′‐N‐ethylcarboxyamidoadenosine (CGS 21680), N ‐[2‐(3,5‐dimethoxyphenyl)ethyl]adenosine (DPMA) and metrifudil were investigated for their ability to prevent the loss of pyramidal CA1 neurons in the hippocampus following 5 min of severe temporary forebrain ischemia in mongolian gerbils. CGS 21680, when administered at 18.7 μmol/kg 30 and 120 min following reperfusion, exhibited highly significant protection against neuronal loss, but was inactive at 5.6 μmol/kg. DPMA, a more potent agonist at A 1 and A 2A receptors, was inactive up to a dose of 19 μmol/kg. Metrifudil (equipotent with CGS 21680 at A 2A >25 times more potent at A 1 ) gave a modest degree of protection at 26 μmol/kg and was inactive at 7.8 μmol/kg. CGS 21680 showed an equal degree of hypothermia at 5.6 and 18.7 μmol/kg, suggesting that this was not the prime mode of action. While the effect of metrifudil may be the result of its higher A 1 receptor affinity, the mode of action of CGS 21680 has not been established; the data, however, suggest that a non‐A 1 non‐A 2A receptor mechanism may possibly be involved. Drug Dev. Res. 39:108–114 © 1997 Wiley‐Liss, Inc.