Effect of Brewer's yeast-induced pyrexia on aminophylline-elicited convulsions in mice.
Theophylline-associated convulsions have been observed most frequently in children with fever, but the mechanism is not fully understood. In this study, we investigated the basic mechanism of aminophylline [theophylline-2-ethylenediamine]-induced convulsions and the effects of Brewer's yeast-induced pyrexia in mice. Diazepam (5-10mg/kg, i.p.), a benzodiazepine receptor agonist, significantly prolonged the onset and significantly decreased the incidence of convulsions induced by aminophylline (350 mg/kg, i.p.). However, the gamma aminobutyric acid (GABA)A receptor agonist muscimol (1-4 mg/kg, i.p.), the GABAB receptor agonist baclofen (2-4 mg/kg, i.p.) and the N-methyl-D-aspartic acid receptor antagonist dizocilpine (0.1-0.3 mg/kg, i.p.) failed to protect against the convulsions. 20% Brewer's yeast (0.02 ml/g, s.c.) increased body temperature by 1.03, and also significantly shortened the onset and significantly increased the incidence of convulsions induced by aminophylline. The anticonvulsant action of diazepam (2.5-10mg/kg, i.p.) on the convulsions induced by aminophylline was reduced by Brewer's yeast-induced pyrexia. The proconvulsant actions of the GABAA receptor antagonists picrotoxin (3-4 mg/kg, i.p.) and pentylenetetrazol (40-60 mg/kg, i.p.) were enhanced by Brewer's yeast. These results suggest that the anticonvulsant action of diazepam against aminophylline is reduced by Brewer's yeast-induced pyrexia, and that GABAA receptors are involved in the aggravation of the convulsions by Brewer's yeast in mice.
Ochi
Rika
R
Department of Clinical Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8530, Japan.
Suemaru
Katsuya
K
Kawasaki
Hiromu
H
Araki
Hiroaki
H
D000628:Aminophylline / Q000009:adverse effects* / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism; D001049:Apnea / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D003292:Convulsants / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000378:metabolism; D010433:Pentylenetetrazole / Q000378:metabolism; D010852:Picrotoxin / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D012441:Saccharomyces cerevisiae / Q000276:immunology; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology
D000628:Aminophylline; D000927:Anticonvulsants; D001993:Bronchodilator Agents; D003292:Convulsants; D003975:Diazepam; D016291:Dizocilpine Maleate; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D018696:Neuroprotective Agents; D010433:Pentylenetetrazole; D010852:Picrotoxin; D058906:Purinergic P1 Receptor Agonists