title: Influence of chronic aminophylline on the anticonvulsant efficacy of phenobarbital and valproate in mice.
abstract: The protective efficacy of phenobarbital (PB, 120 min before testing) and valproate (VPA, 30 min before testing) alone or combined with aminophylline (a single dose of 50 mg/kg, 3-day or 14-day administration twice daily 50 mg/kg at 8.00 a.m. and 8.00 p.m.) was evaluated against maximal electroshock-induced seizures (MES) in male mice. All drugs were given intraperitoneally (i.p.), and the protection provided by PB and VPA was evaluated as the respective ED50 value (in mg/kg). Aminophylline in a single dose of 50 mg/kg (30 min before electroconvulsions) distinctly reduced the protective efficacy of both PB and VPA, reflected by the increase in the respective ED50 values from 22 to 31 mg/kg (p < 0.001) for PB and from 247 to 281 mg/kg (p < 0.001) for VPA. After administration of aminophylline for 3 days (electroshock was performed 30 min after the last aminophylline injection), the respective ED50 values for PB and VPA were 29.5 (p < 0.01) and 269 mg/kg (p < 0.01 vs. saline-treated animals). Chronic treatment with aminophylline (14 days) resulted in further impairment of the protective activity of PB and VPA. Specifically, the ED50 value of PB was 39 mg/kg (p < 0.05 vs. PB+single injection of aminophylline) and that of VPA was 318 mg/kg (p < 0.01 vs VPA+single injection of aminophylline). Plasma levels of both PB and VPA were not affected by chronic aminophylline; moreover, the plasma level of theophylline was even lower after chronic aminophylline as compared with single aminophylline administration.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, School of Agriculture, Medical School, Lublin, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Wlaz
authors.forename: Z
authors.initials: Z
authors.lastname: Rolinski
authors.forename: Z
authors.initials: Z
authors.lastname: Kleinrok
authors.forename: S J
authors.initials: SJ
authors.lastname: Czuczwar
mesh_terms: D000628:Aminophylline / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004597:Electroshock; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D010634:Phenobarbital / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D012640:Seizures / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D014635:Valproic Acid / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
chemical_list: D000628:Aminophylline; D014635:Valproic Acid; D010634:Phenobarbital