title: Caffeine-induced seizures: apparent proconvulsant action of N-ethyl carboxamidoadenosine (NECA).
abstract: 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.
authors.affiliation: Laboratory of Clinical Studies, National Institute on Alcohol Abuse & Alcoholism, DICBR, Bethesda, MD 20892.
authors.forename: P F
authors.initials: PF
authors.lastname: Morgan
authors.forename: M J
authors.initials: MJ
authors.lastname: Durcan
mesh_terms: 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
chemical_list: D000927:Anticonvulsants; D011983:Receptors, Purinergic; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; D002110:Caffeine; D000241:Adenosine