The Role of the Adenosine System in Epilepsy and its Comorbidities

Epilepsy is one of the most serious and common chronic neurological conditions, characterised by recurrent hypersynchronous electrical activity in the brain that lead to seizures. Despite over 50 million people being affected worldwide, only ~70% of people with epilepsy have their seizures successfully controlled with current pharmacotherapy, and many experience significant psychiatric and physical comorbidities. Adenosine, a ubiquitous purine metabolite, is a potent endogenous anti-epileptic substance that can abolish seizure activity via the adenosine A G protein-coupled receptor (A R). A R activation decreases seizure activity in animal models, including models of drug-resistant epilepsy. Recent advances have increased our understanding of epilepsy comorbidities, highlighting the potential for adenosine receptors to modulate epilepsy-associated comorbidities, including cardiovascular dysfunction, sleep, and cognition. This review provides an accessible resource of the current advances in understanding the adenosine system as a therapeutic target for epilepsy and epilepsy-associated comorbidities.