BACKGROUND: Theophylline overdose can produce seizures (sz) which may be associated with significant long-term neurological sequelae. The mechanism by which theophylline produces szs is unclear but may be related to either antagonism at the GABAA receptor or the adenosine receptor. Flumazenil (flz) is known to have anti-convulsant effects at supratherapeutic doses; this may be related to effects on adenosine re-uptake or action as partial benzodiazepine agonist. OBJECTIVE: To examine the effect of flz on sz production in a mouse model of aminophylline poisoning. METHODS: Male CD-1 mice weighing between 20- 35 g were injected ip with aminophylline and either flz or sterile water. Each groups had between 8-10 mice. Flz was studied at doses ranging from 0.1 - 0.4 mg/kg using 2 doses of aminophylline. Outcome measures were presence of sz and time to sz. RESULTS: The data obtained for doses of 250 mg aminophylline/kg and 240 mg aminophylline/kg are shown in the table below. CONCLUSION: In this animal model of aminophylline toxicity, flz appears to attenuate both the number of animals with szs as well as to prolong the time initial szs occur post-exposure.

Table 1
Full size table