Adenosine A(1) receptor blockage mediates theophylline-associated seizures

作者：Fukuda Mitsumasa^*; Suzuki Yuka; Hino Hitomi; Kuzume Kazuyo; Morimoto Takehiko; Ishii Eiichi

来源：Epilepsia, 2010, 51(3): 483-487.

DOI：10.1111/j.1528-1167.2009.02382.x

• Status epilepticus
• Adenosine
• Seizure termination
• Young age
• Fever

P>Theophylline-associated seizures (TAS) often progress to prolonged or treatment-resistant convulsions. Theophylline is a nonselective adenosine receptor antagonist. Adenosine is an endogenous anticonvulsant that can terminate seizures. Fever and young age have been reported to be risk factors for TAS. To elucidate the mechanism of TAS, we investigated the effect of theophylline and adenosine receptor ligands on hyperthermia-induced seizures in juvenile rats. The treatment dose of theophylline or control saline was injected intraperitoneally 1 h before hyperthermia-induced seizures. The seizure threshold in the theophylline group was significantly lower and seizure duration was significantly longer than those in the control group. The addition of a selective adenosine A(1) receptor agonist and an adenosine kinase inhibitor completely counteracted the effects of theophylline. Moreover, a selective A(1) antagonist caused a significantly longer seizure duration compared with the control. These findings suggest that blockage of the adenosine A(1) receptor is the main cause of TAS.

• 出版日期2010-3