Adenosinergic Drugs, an Alternative Treatment for Status Epilepticus

Status epilepticus (SE) is one of the medical emergency conditions that require rapid treatment because of its high morbidity and mortality. However, treatment of SE is limited and medications must be administered almost immediately after the onset of the seizure to help alleviate the symptoms and prevent neurological damage. Traditionally, benzodiazepines including diazepam have been the first line of defense against SE but the effectiveness of diazepam decreases drastically with increasing time of seizure duration. In the present experiment, the additive effect of adenosine analogs are studied in lithium-pilocarpine induced SE in rats, which represents various clinical and neuropathological features of human temporal lobe epilepsy. This protocol will include a series of experiments in which, male Wistar rats will be injected with lithium, 18-20h before pilocarpine to induce self-sustaining SE within 30-60min. Later, the time point where diazepam loses its effectiveness in preventing the seizures will be determined. Additive effect of various adenosine analogs will be studied at this time point. Adenosinergic drugs are hypothesized to suppress seizures, and in turn reduce neuropathological complications associated with SE. Thus, adenosine-related drugs could become an effective alternate approach for treatment of intractable seizures.