Potent convulsant actions of the adenosine receptor antagonist, xanthine amine congener (XAC).
The convulsant properties of xanthine amine congener (XAC, 8-(4-(2-aminoethyl)-aminocarboxylmethyloxy)phenyl-1,3-dipropylxant hine) are compared to those of caffeine. Male Swiss albino mice were infused with convulsants through a lateral tail vein. Convulsion thresholds (i.e. the amount of convulsants required to elicit convulsions) of 39.8 +/- 2.0 mg/kg (n = 10) and 109.8 +/- 2.3 mg/kg (n = 10) were calculated for XAC and caffeine respectively. Pretreatment of animals with the adenosine receptor agonists 2-chloroadenosine, N6-cyclohexyladenosine or 5'-N-ethylcarboxamido-adenosine (1 mg/kg, i.p., 20 minutes prior to infusion) significantly decreased the seizure threshold of both XAC and caffeine. The adenosine uptake blockers, 6-nitrobenzylthioinosine or dipyridamole (0.25 mg/kg, i.p., 20 minutes prior to infusion) did not significantly affect the seizure threshold to either XAC or caffeine. The benzodiazepine agonist diazepam (5 mg/kg, i.p., 20 minutes prior to infusion) significantly increased the seizure threshold to both XAC (p less than 0.05) and caffeine (p less than 0.01), whereas the benzodiazepine antagonist Ro 15-1788 (10 mg/kg, i.p., 20 minutes prior to infusion) significantly increased the seizure threshold to caffeine (p less than 0.01), but not XAC. The results suggest that actions at benzodiazepine receptors may be a tenable hypothesis to explain the convulsant actions of caffeine, but not those of XAC.
Morgan
P F
PF
Biological Psychiatry Branch, N.I.M.H. Bethesda, MD 20892.
Deckert
J
J
Jacobson
K A
KA
Marangos
P J
PJ
Daly
J W
JW
D000818:Animals; D002110:Caffeine / Q000633:toxicity*; D003292:Convulsants; D003975:Diazepam / Q000494:pharmacology; D004176:Dipyridamole / Q000633:toxicity; D008297:Male; D051379:Mice; D058914:Purinergic Antagonists; D011897:Random Allocation; D012640:Seizures / Q000139:chemically induced*; D013806:Theophylline / Q000633:toxicity; D014970:Xanthines / Q000633:toxicity*
D003292:Convulsants; D058914:Purinergic Antagonists; D014970:Xanthines; D002110:Caffeine; D004176:Dipyridamole; C051869:8-(4-((2-aminoethyl)aminocarbonylmethyloxy)phenyl)-1,3-dipropylxanthine; D013806:Theophylline; D003975:Diazepam