Effects of aminophylline and 2-chloroadenosine on seizures produced by pilocarpine in rats: morphological and electroencephalographic correlates.
The effects of 2-chloroadenosine, aminophylline, bicuculline, beta-carboline-3-carboxylic acid methylester and Ro 15-1788 on seizures produced by pilocarpine were examined in rats. In animals pretreated with aminophylline at doses of 25-100 mg/kg, non-convulsant dose of pilocarpine, 100 mg/kg, resulted in severe motor limbic seizures, which rapidly developed into the status epilepticus. Electroencephalographic monitoring showed progressive evolution of seizure activity with initial high-voltage fast activity followed by high-voltage spiking and electrographic seizures. Morphological analysis of frontal forebrain sections with light microscopy demonstrated widespread damage to the hippocampal formation, thalamus, amygdala, olfactory cortex, substantia nigra and neocortex. Bicuculline, 2 mg/kg, beta-carboline-3-carboxylic acid methylester, 5 mg/kg, and Ro 15-1788, 50 mg/kg, did not augment seizures produced by pilocarpine, 100 mg/kg. 2-Chloroadenosine, 5 and 10 mg/kg, blocked the appearance of behavioral and electrographic seizures produced by pilocarpine, 380 mg/kg, and prevented the occurrence of brain damage. The results indicate that purinergic mechanisms are involved in the buildup of pilocarpine-induced convulsions and seizure-related brain damage in rats.
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology*; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D002243:Carbolines / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D004569:Electroencephalography; D005442:Flumazenil; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010862:Pilocarpine; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*
D001570:Benzodiazepinones; D002243:Carbolines; D003292:Convulsants; D010862:Pilocarpine; D015762:2-Chloroadenosine; D000628:Aminophylline; D005442:Flumazenil; C036150:beta-carboline-3-carboxylic acid methyl ester; D000241:Adenosine; D001640:Bicuculline