{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T11:35:43Z","timestamp":1760441743640,"version":"3.40.5"},"reference-count":70,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The use of many antiseizure medications (ASMs) is limited due to pharmacoresistance and dose\u2010limiting side effects, suggesting an unmet need for novel therapeutic approaches. The neuropeptide galanin reduces seizures in several preclinical seizure and epilepsy models, but its clinical utility is limited due to rapid metabolism and poor blood\u2013brain barrier penetration. The lead galanin analog 810\u20132 is systemically bioavailable and reduces seizures when administered alone. Further development of this analog, with the potential for use as an add\u2010on therapy in patients with epilepsy, requires a better understanding of the use of this analog in combination with approved ASMs. We sought to evaluate 810\u20132 in combination with commonly used ASMs in rodent models of seizures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The mouse 6\u2010Hz seizure assay was used to test efficacy of 810\u20132 in combination with levetiracetam (LEV), valproic acid (VPA), or lacosamide (LCM) using a 1:1 dose ratio in isobolographic studies. Further characterization was performed for the combination of 810\u20132 and LEV in the mouse corneal kindling and rat 6\u2010Hz assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Whereas the combination of 810\u20132 with VPA and LCM yielded additive interactions, the combination of 810\u20132 with LEV demonstrated a synergistic interaction in the mouse 6\u2010Hz assay. Supra\u2010additive effects were also observed in the mouse corneal kindling and rat 6\u2010Hz assays for this combination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>The combination of 810\u20132 with LEV suggests the potential for this galanin analog to be further developed as an add\u2010on therapy for patients with epilepsy, particularly when coadministered with LEV.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17420","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T06:49:28Z","timestamp":1664520568000},"page":"3090-3099","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synergistic effects of the galanin analog 810\u20132 with the antiseizure medication levetiracetam in rodent seizure models"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1510-0405","authenticated-orcid":false,"given":"Cameron S.","family":"Metcalf","sequence":"first","affiliation":[{"name":"Epilepsy Therapy Screening Program Contract Site, Department of Pharmacology and Toxicology, College of Pharmacy University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saurabh","family":"Gagangras","sequence":"additional","affiliation":[{"name":"Epilepsy Therapy Screening Program Contract Site, Department of Pharmacology and Toxicology, College of Pharmacy University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grzegorz","family":"Bulaj","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-4408","authenticated-orcid":false,"given":"H. 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