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Influence of Chronic Aminophylline on the Anticonvulsant Efficacy of Phenobarbital and Valproate in Mice
Author(s) -
Wlaż Piotr,
Rolinski Zbigniew,
Kleinrok Zdzislaw,
Czuczwar Stanistaw J.
Publication year - 1993
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1993.tb02426.x
Subject(s) - aminophylline , anticonvulsant , phenobarbital , medicine , pharmacology , epilepsy , anesthesia , psychiatry
Summary: 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 ED 50 value (in mg/kg). Aminophylline in a single dose of 50 mg/kg (30 min before electro‐convulsions) distinctly reduced the protective efficacy of both PB and VPA, reflected by the increase in the respective ED 50 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 ED 50 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 ED 50 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. The results of the present study provide evidence that no tolerance exists to aminophylline‐induced impairment of antiepileptic drug efficacy; moreover, this phenomenon may even be increased with chronic aminophylline administration.