Differential effects of various xanthines on pentylenetetrazole-induced seizures in rats: an EEG and behavioural study.
The present study deals with the EEG (electroencephalogram) and behavioural effects of a subconvulsant dose (30 mg/kg i.p.) of pentylenetetrazole in freely moving rats pretreated (100 mg/kg p.o., 1 h before pentylenetetrazole) with two classic (theophylline and caffeine) and two new (enprofylline and isbufylline) xanthines. In rats treated with vehicle, pentylenetetrazole caused a slight desynchronization of the EEG, characterized by periods of 'wave discharges', and 'spike-and-wave discharge complexes'. In rats pretreated with xanthines (theophylline or caffeine) pentylenetetrazole produced a dramatic increase in ictal seizures with the appearance of continuous spikes; concomitantly animals experienced myoclonic jerks (100%) and in some cases (ca. 20%) the animals died. In contrast, in enprofylline-pretreated rats, pentylenetetrazole induced only brief periods of wave discharges and spike-and-wave discharge complexes whose duration was significantly reduced compared to that of controls, although these discharges were associated with mild epileptic behaviour. When isbufylline-pretreated rats were challenged with pentylenetetrazole, the EEG was characterized by a short run of wave discharges (whose duration was shorter than that of other groups). No enprofylline- or isbufylline-treated rats developed seizures or died. In conclusion, only xanthines with strong adenosine A1 receptor antagonism (theophylline and caffeine) markedly enhance the EEG and behavioural effects of a subconvulsive dose of pentylenetetrazole. The present experimental approach could be used to evaluate the pro-convulsive potential of new xanthine derivatives.
D015056:1-Methyl-3-isobutylxanthine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects*; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013806:Theophylline / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010276:Parasympatholytics; D014970:Xanthines; D002110:Caffeine; C058878:isbufylline; D013806:Theophylline; C034347:enprofylline; D000241:Adenosine; D015056:1-Methyl-3-isobutylxanthine; D010433:Pentylenetetrazole