Unexpected neuroprotection observed with the adenosine A2A receptor agonist CGS 21680

✍ Scribed by Malcolm J. Sheardown; Lars J.S. Knutsen

• Book ID: 102655978
• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 586 KB
• Volume: 39
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/(sici)1098-2299(19960901)39:1<108::aid-ddr8>3.0.co;2-j

✦ Synopsis

The selective adenosine AZA receptor agonists 2-[p-(2-~arboxethyl)phenylethylamino]-5 '-N-ethylcarboxyamidoadenosine (CGS 21 680), N-[2-(3,5-dimethoxyphenyl)ethyl]adenosine (DPMA) and metrifudil were investigated for their ability to prevent the loss of pyramidal CAI neurons in the hippocampus following 5 min of severe temporary forebrain ischemia in mongolian gerbils. CGS 21 680, when administered at 18.7 ymolikg 30 and 120 min following reperfusion, exhibited highly significant protection against neuronal loss, but was inactive at 5.6 pmol/kg. DPMA, a more potent agonist at A1 and A ~A receptors, was inactive up to a dose of 19 pmol/kg. Metrifudil (equipotent with CGS 21 680 at >25 times more potent at Al) gave a modest degree of protection at 26 pmol/kg and was inactive at 7.8 pmol/kg. CGS 21 680 showed an equal degree of hypothermia at 5.6 and 18.7 pmol/kg, suggesting that this was not the prime mode of action. While the effect of metrifudil may be the result of its higher A1 receptor affinity, the mode of action of CGS 21680 has not been established; the data, however, suggest that a non-A, non-AZA receptor mechanism may possibly be involved.