Pharmacological studies on mechanisms of aminophylline-induced seizures in rats.
In the present study, the possible role of free radicals in aminophylline-induced seizures was evaluated in albino rats. Aminophylline (theophylline in ethylene diamine; 50 - 300 mg/kg) induced convulsions in rats in a dose-dependent manner, and both incidence of seizure and mortality were maximum at 300 mg/kg. Conventional anti-epileptics, diphenylhydantoin and dizocilpine, as well as adenosine agonists were ineffective in antagonizing these seizures. On the other hand, phosphodiesterase inhibitors, pentoxyphylline and rolipram, showed insignificant seizurogenic effects. Pretreatment with antioxidants (ascorbic acid, alpha-tocopherol, and melatonin) showed differential attenuating effects on aminophylline seizures and lethality. Further, prior administration of 1-buthionine sulfoxamine (BSO, glutathione depletor) and triethyltetramine (TETA, superoxide dismutase inhibitor), precipitated seizures and enhanced lethality in response to subthreshold doses of aminophylline. The present results suggested of the possible involvement of oxidative stress during aminophylline-induced seizures.
Ray
Arunabha
A
Department of Pharmacology and Clinical Research Centre, Vallabhbhai Patel Chest Institute University of Delhi, Delhi 110 007, India. arunabha14@yahoo.co.in
Gulati
Kavita
K
Anand
Seema
S
Vijayan
V K
VK
D000628:Aminophylline / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals; D008297:Male; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D010431:Pentoxifylline / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D020889:Rolipram / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced*; D014266:Trientine / Q000494:pharmacology
D000927:Anticonvulsants; D000975:Antioxidants; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D005609:Free Radicals; D016877:Oxidants; D010726:Phosphodiesterase Inhibitors; D017382:Reactive Oxygen Species; D000628:Aminophylline; D019328:Buthionine Sulfoximine; D010672:Phenytoin; D016291:Dizocilpine Maleate; D020889:Rolipram; D010431:Pentoxifylline; D014266:Trientine