title: Effect of heat exposure on aminophylline-induced convulsions in mice.
abstract: Theophylline-associated convulsions are frequently exacerbated by fever, but the mechanisms behind it are still not completely understood. We investigated whether N-methyl-D-aspartic acid (NMDA) and gamma aminobutyric acid (GABA) receptors are involved in aminophylline (theophylline-2-ethylenediamine)-induced convulsions that are augmented by heat exposure-induced hyperthermia in mice. Mice exposed to 33 °C temperatures for 2 h had significantly increased body temperature (0.94 °C). Heat exposure significantly decreased time required for the onset of convulsions induced by an intraperitoneal (i.p.) injection of aminophylline (300 mg/kg). The shortened time for onset of convulsions was blocked by the NMDA receptor antagonist dizocilpine (0.1, 0.3 mg/kg, i.p.). However, the GABA(A) receptor agonist muscimol (1, 2 mg/kg, i.p.) did not have any effect. The pro-convulsant action of NMDA (100-125 mg/kg, i.p.) was enhanced by the heat exposure of 33 °C. However, the pro-convulsant actions of picrotoxin (3-4 mg/kg, i.p.), a GABA(A) receptor antagonist, were not affected by increased temperatures. These results suggest that NMDA receptors in the brain play a role in aminophylline-induced convulsions, which are augmented by heat exposure-induced hyperthermia in mice.
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Ochi
authors.forename: Katsuya
authors.initials: K
authors.lastname: Suemaru
authors.forename: Shinichi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Takumi
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Kenshi
authors.initials: K
authors.lastname: Takechi
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Araki
mesh_terms: D000628:Aminophylline / Q000633:toxicity*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005334:Fever; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced*; D013806:Theophylline / Q000097:blood
chemical_list: D009118:Muscimol; D000628:Aminophylline; D016291:Dizocilpine Maleate; D013806:Theophylline