DIFFERENTIAL-EFFECTS OF VARIOUS XANTHINES ON PENTYLENETETRAZOLE-INDUCED SEIZURES IN RATS - AN EEG AND BEHAVIORAL-STUDY

被引:44
作者
CUTRUFO, C
BORTOT, L
GIACHETTI, A
MANZINI, S
机构
[1] Menarini Ricerche Sud, Department of Pharmacology, 00040 Pomezia, Roma
关键词
XANTHINES; SEIZURES; PENTYLENETETRAZOLE; EEG (ELECTROENCEPHALOGRAM); ADENOSINE;
D O I
10.1016/0014-2999(92)90454-C
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 Al 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.
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收藏
页码:1 / 6
页数:6
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