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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\u2010epileptic substance that can abolish seizure activity via the adenosine A\n                      <jats:sub>1<\/jats:sub>\n                      G protein\u2010coupled receptor. Activation of A\n                      <jats:sub>1<\/jats:sub>\n                      receptors decreases seizure activity in animal models, including models of drug\u2010resistant epilepsy. Recent advances have increased our understanding of epilepsy comorbidities, highlighting the potential for adenosine receptors to modulate epilepsy\u2010associated 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\u2010associated comorbidities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LINKED ARTICLES<\/jats:title>\n                    <jats:p>\n                      This article is part of a themed issue Therapeutic Targeting of G Protein\u2010Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v181.14\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v181.14\/issuetoc<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.16094","type":"journal-article","created":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T20:20:07Z","timestamp":1681935607000},"page":"2143-2157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["The role of the adenosine system in epilepsy and its comorbidities"],"prefix":"10.1111","volume":"181","author":[{"given":"Jo\u2010Anne","family":"Baltos","sequence":"first","affiliation":[{"name":"Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences Monash University  Parkville Victoria 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