Influence of adenosine agonists and antiepileptic drugs on theophylline-induced seizures in rats.
Seizures is a major toxicity of theophylline. The mechanism of theophylline-induced seizures is not known, but antagonism at adenosine receptors may be a possibility. The effect of pretreatment with different doses of adenosine (100, 500 and 1000 mg/kg, i.p.), and the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA), 1, 5 and 10 mg/kg, i.p., was studied against seizures induced by theophylline in rats. Both these drugs, at all dose levels tested, failed to protect theophylline seizures. Thus adenosinergic system is unlikely to be involved in mediating the convulsant action of theophylline. On the other hand, the conventional antiepileptic drugs, i.e. diazepam (4 mg/kg), sodium valproate (300 mg/kg) and phenobarbitone (50 mg/kg), but not carbamazepine, afforded some protection. The modification of course of seizures, by the antiepileptic drugs suggests the involvement of some other alternate mechanism in theophylline-induced seizures.
Gupta
Y K
YK
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi.
Malhotra
J
J
D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013806:Theophylline / Q000009:adverse effects
D000889:Anti-Arrhythmia Agents; D000927:Anticonvulsants; D010726:Phosphodiesterase Inhibitors; D058906:Purinergic P1 Receptor Agonists; C048599:N(6)-cyclopentyladenosine; D013806:Theophylline; D000241:Adenosine