Activation of adenosine A1 receptors underlies anticonvulsant effect of CGS21680.
Focal injection of the adenosine A2A receptor agonist CGS21680 (2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethyl-carboxamidoaden osine) in the rat prepiriform cortex produced a reduction in the severity of bicuculline methiodide-induced motor seizures. The anticonvulsant effect of CGS21680 exhibited dose-dependency and modest potency (ED50 = 605 +/- 47 pmol/rat). Pharmacological characterization of the anticonvulsant response in the prepiriform cortex revealed a significant correlation between the potency of adenosine analogs as anticonvulsants and their respective affinities for adenosine A1 receptors in vitro. These results indicate that the low affinity of CGS21680 for adenosine A1 receptors is sufficient to account for the anticonvulsant activity of this compound in the rat prepiriform cortex.
Zhang
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College of Pharmacy, Oregon State University, Corvallis 97331.
Franklin
P H
PH
Murray
T F
TF
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D014970:Xanthines / Q000494:pharmacology
D000927:Anticonvulsants; D000959:Antihypertensive Agents; D010627:Phenethylamines; D018047:Receptors, Purinergic P1; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D001640:Bicuculline