Caffeine-induced seizures: apparent proconvulsant action of N-ethyl carboxamidoadenosine (NECA).
The effect of adenosine agonist pretreatment on the seizure activity of caffeine was investigated in NIH Swiss mice. The seizure ED50 of caffeine alone was determined to be 223 mg/kg and this was reduced to 68 mg/kg following pretreatment with 0.30 mg/kg N-ethyl carboxamidoadenosine (NECA). Additionally, NECA dose-dependently increased the seizure potency of 100 mg/kg caffeine (a dose which is normally subconvulsant). A proconvulsant effect of NECA was also detected following intracerebroventricular administration of 2.5 ug NECA, however the same doses of N6-cyclohexyladenosine (CHA) and 2-chloroadenosine (2 C1-ADO) did not precipitate seizures. The data reveal proconvulsant actions of both peripherally and centrally administered NECA towards caffeine-induced seizures. Such actions need to be reconciled with the general anticonvulsant action of adenosine and adenosine agonists.
Morgan
P F
PF
Laboratory of Clinical Studies, National Institute on Alcohol Abuse & Alcoholism, DICBR, Bethesda, MD 20892.
Durcan
M J
MJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D000927:Anticonvulsants; D002110:Caffeine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002552:Cerebral Ventricles / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D011292:Premedication; D011983:Receptors, Purinergic / Q000187:drug effects; D012044:Regression Analysis; D012640:Seizures / Q000139:chemically induced* / Q000401:mortality
D000927:Anticonvulsants; D011983:Receptors, Purinergic; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; D002110:Caffeine; D000241:Adenosine