{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:17:29Z","timestamp":1792167449306,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,7,10]],"date-time":"2017-07-10T00:00:00Z","timestamp":1499644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Although drugs targeting the cannabinoid system (e.g., <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>1 receptor agonists) display anticonvulsant efficacy in adult animal models of seizures\/epilepsy, they remain unexplored in developing animal models. However, cannabinoid system functions emerge early in development, providing a rationale for targeting this system in neonates. We examined the therapeutic potential of drugs targeting the cannabinoid system in three seizure models in developing rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Postnatal day (P) 10, Sprague\u2013Dawley rat pups were challenged with the chemoconvulsant methyl\u20106,7\u2010dimethoxy\u20104\u2010ethyl\u2010beta\u2010carboline\u20103\u2010carboxylate (<jats:styled-content style=\"fixed-case\">DMCM<\/jats:styled-content>) or pentylenetetrazole (<jats:styled-content style=\"fixed-case\">PTZ<\/jats:styled-content>), after treatment with either <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>1\/2 mixed agonist (<jats:styled-content style=\"fixed-case\">WIN<\/jats:styled-content> 55,212\u20102), <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>1 agonist (<jats:styled-content style=\"fixed-case\">arachidonyl\u20102\u2032\u2010chloroethylamide [ACEA]<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>2 agonist (<jats:styled-content style=\"fixed-case\">HU<\/jats:styled-content>\u2010308), <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>1 antagonist (<jats:styled-content style=\"fixed-case\">AM<\/jats:styled-content>\u2010251), <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>2 antagonist (<jats:styled-content style=\"fixed-case\">AM<\/jats:styled-content>\u2010630), fatty acid amide hydrolase inhibitor (<jats:styled-content style=\"fixed-case\">URB<\/jats:styled-content>\u2010597), or G protein\u2013coupled receptor 55 agonist (O\u20101602). P20 Sprague\u2013Dawley pups were challenged with <jats:styled-content style=\"fixed-case\">DMCM<\/jats:styled-content> after treatment with <jats:styled-content style=\"fixed-case\">WIN<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> ACEA<\/jats:styled-content>, or <jats:styled-content style=\"fixed-case\">URB<\/jats:styled-content>. Finally, after pretreatment with <jats:styled-content style=\"fixed-case\">WIN<\/jats:styled-content>, P10 Sprague\u2013Dawley rats were challenged against acute hypoxia\u2010induced seizures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mixed <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>1\/2 agonist and the <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>1\u2010specific agonist, but no other drugs, displayed anticonvulsant effects against clonic seizures in the <jats:styled-content style=\"fixed-case\">DMCM<\/jats:styled-content> model. By contrast, both <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>2 antagonism increased seizure severity. Similarly, we found that the <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>1\/2 agonist displayed antiseizure efficacy against acute hypoxia\u2010induced seizures (automatisms, clonic and tonic\u2013clonic seizures) and tonic\u2013clonic seizures evoked by <jats:styled-content style=\"fixed-case\">PTZ<\/jats:styled-content>. Anticonvulsant effects were seen in P10 animals but not P20 animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Early life seizures represent a significant cause of morbidity, with 30\u201340% of infants and children with epilepsy failing to achieve seizure remission with current pharmacotherapy. Identification of new therapies for neonatal\/infantile epilepsy syndromes is thus of high priority. These data indicate that the anticonvulsant action of the <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content> system is specific to <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>1 receptor activation during early development and provide justification for further examination of <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>1 receptor agonists as novel antiepileptic drugs targeting epilepsy in infants and children.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13842","type":"journal-article","created":{"date-parts":[[2017,7,10]],"date-time":"2017-07-10T06:34:42Z","timestamp":1499668482000},"page":"1593-1602","source":"Crossref","is-referenced-by-count":53,"title":["Anticonvulsant effect of cannabinoid receptor agonists in models of seizures in developing rats"],"prefix":"10.1111","volume":"58","author":[{"given":"Megan N.","family":"Huizenga","sequence":"first","affiliation":[{"name":"Pharmacology &amp; Physiology Georgetown University Washington District of Columbia U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Wicker","sequence":"additional","affiliation":[{"name":"Pharmacology &amp; 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