Adenosine Receptors are not Involved in Theophylline-Induced Seizures

Abstract

One of the most dangerous aspects of theophylline toxicity is seizures. A review of the literature suggests that current anticonvulsant therapy remains far from optimal. As it is known that some of the pharmacologic effects of theophylline occur via antagonism of the adenosine A₁ receptor, we tested the hypothesis that agonists acting at the adenosine A₁ receptor can inhibit seizures caused by toxic doses of theophylline in mice. Dose-response curves were constructed for the ability of theophylline to produce tonic seizures in animals pre-treated with vehicle or several adenosine A₁ receptor agonists. The LD₅₀ (95% CI) for each dose-response curve was calculated. The results of these experiments showed that pretreatment with the direct-acting adenosine A₁ agonists carbamazepine and cyclohexyladenosine and the indirect-acting agonist dipyridamole each failed to inhibit the ability of theophylline to cause tonic seizures (p > 0.05). Failure of these drugs to protect against theophylline-induced seizures suggests these seizures are produced by other mechanisms. Based on our results, adenosine A₁ agonists, such as carbamazepine, appear to offer no therapeutic benefit in the treatment of theophylline-induced seizures.

Key Words:

• seizures
• toxicity
• theophylline
• carbamazepine
• adenosine receptors
• mice