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 similar to 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(1) G protein-coupled receptor. Activation of A(1) receptors 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.

Automated summary

Epilepsy, a serious neurological condition, affects millions of people worldwide. Current pharmacotherapy only successfully controls seizures in about 70% of epilepsy patients, and many suffer from psychiatric and physical comorbidities. Adenosine, a natural substance, has shown potential as an anti-epileptic agent through its receptor activation. Recent advances have also shown that adenosine receptors can modulate epilepsy-associated comorbidities. This review provides an accessible resource on the use of the adenosine system as a therapeutic target for epilepsy and its associated comorbidities.