Blockade by 1,3-dipropyl-8-cyclopentylxanthine (CPX) of purine protection against kainate neurotoxicity.
The adenosine A1 receptor selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (CPX) has been administered systemically to rats together with the neurotoxin kainic acid. At the lower doses of CPX tested, 10 and 50 micrograms/kg, which were sufficient to prevent the neuroprotective activity of exogenous agonists, there was no exacerbation of the neuronal damage. At 250 micrograms/kg, some enhancement of damage was found, which was also produced by 8-(p-sulphophenyl)theophylline, a non-selective xanthine which does not cross the blood-brain barrier. The results are consistent with the involvement of a central A1 receptor in the neuroprotective activity of purines, and suggest that blockade of a peripheral adenosine receptor, possibly of the A2 type, may increase neuronal damage.
Macgregor
D G
DG
Dept. of Pharmacology, University of Glasgow, UK.
Stone
T W
TW
D000818:Animals; D007608:Kainic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
D058915:Purinergic P1 Receptor Antagonists; D011687:Purines; D018047:Receptors, Purinergic P1; D014970:Xanthines; D010660:Phenylisopropyladenosine; C031433:8-(4-sulfophenyl)theophylline; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; C028322:8-phenyltheophylline; D007608:Kainic Acid