{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T21:48:54Z","timestamp":1769896134346,"version":"3.49.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Recently, a series of N\u2010 and C\u2010modified hemorphins have been synthesized, characterized and evaluated for their antibacterial potency. These analogues included amino acids such as cysteine (Cys), glutamic acid (Glu), and histidine (His), as well as 1\u2010adamantanecarboxylic acid (Adam), and niacin (nicotinic acid) (Nic). The current study aimed to explore the anti\u2010seizure potential of these compounds in mice. The role of opioid receptors (ORs) in their mechanism of action was evaluated both pharmacologically and through\n                    <jats:italic>in silico<\/jats:italic>\n                    methods. A battery of tests were used, including the 6\u2010Hz and maximal electroshock seizures (MES) tests, as well as kainate (KA)\u2010induced status epilepticus (SE), pentylenetetrazol (PTZ) and corneal kindling models. The intracerebroventricular infusion of peptide analogues, specifically those containing Cys, Glu, His and Adam but not Nic, showed reduced psychomotor seizures and seizure spread. The effective dosages were as follows:\n                    <jats:bold>C\u2010V<\/jats:bold>\n                    (25\u2009\u03bcg\/5\u2009\u03bcl\u20146\u2009Hz and MES),\n                    <jats:bold>H\u2010V<\/jats:bold>\n                    (6 and 12\u2009\u03bcg\/5\u2009\u03bcl\u20146\u2009Hz and MES),\n                    <jats:bold>AC\u2010V<\/jats:bold>\n                    (12\u2009\u03bcg\/5\u2009\u03bcl\u2014MES) and\n                    <jats:bold>AH\u2010V<\/jats:bold>\n                    (25\u2009\u03bcg\/5\u2009\u03bcl\u20146\u2009Hz). The efficacy of the compounds in preventing clonic seizures in PTZ\u2010kindled mice was observed, except\n                    <jats:bold>NCH7<\/jats:bold>\n                    . Furthermore,\n                    <jats:bold>C\u2010V<\/jats:bold>\n                    and\n                    <jats:bold>AC\u2010V<\/jats:bold>\n                    were found to be effective in corneal\u2010kindled mice and\n                    <jats:bold>C\u2010V<\/jats:bold>\n                    against the KA\u2010induced SE. Naloxone blocked the anti\u2010seizure effect of\n                    <jats:bold>C\u2010V<\/jats:bold>\n                    and\n                    <jats:bold>AC\u2010V,<\/jats:bold>\n                    which was also confirmed by docking analysis. Our findings suggest that insertion of Cys and Glu (\n                    <jats:bold>C\u2010V<\/jats:bold>\n                    and\n                    <jats:bold>AC\u2010V<\/jats:bold>\n                    ) and Cys, Adam, and Glu (\n                    <jats:bold>AC\u2010V<\/jats:bold>\n                    ) enhances the potential of these novel hemorphin analogues as effective anti\u2010seizure agents.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70209","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T06:20:36Z","timestamp":1766470836000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological Evaluation of Novel N\u2010 and C\u2010Modified Peptide Analogues of VV\u2010hemorphin\u20105 and VV\u2010hemorphin\u20107 as Potential Agents With Anti\u2010Seizure Activity"],"prefix":"10.1002","volume":"87","author":[{"given":"Jana","family":"Tchekalarova","sequence":"first","affiliation":[{"name":"Institute of Neurobiology Bulgarian Academy of Sciences Sofia Bulgaria"},{"name":"Department of Organic Chemistry University of Chemical Technology and Metallurgy Sofia Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miroslav","family":"Rangelov","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry with Centre Of Phytochemistry Bulgarian Academy of Sciences Sofia Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadezhda","family":"Todorova","sequence":"additional","affiliation":[{"name":"Institute of Biodiversity and Ecosystem Research Bulgarian Academy of Sciences Sofia Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsveta","family":"Stoyanova","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology Bulgarian Academy of Sciences Sofia Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petar","family":"Todorov","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry University of Chemical Technology and Metallurgy Sofia 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