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In the present study, the cis forms of these compounds were tested and compared with their trans isomers in seizure and nociception tests in mice. The cis\u2010<jats:bold>H5\u2010CA<\/jats:bold> and <jats:bold>H7\u2010CA<\/jats:bold> compounds showed efficacy against psychomotor seizures, whereas the trans isomers were ineffective. Both the cis and trans KA isomers were ineffective in the 6\u2010Hz test. In the maximal electroshock (MES) test, the cis isomers showed superior antiseizure activity to the trans forms of CA and KA conjugates, respectively. The suppression of seizure propagation by cis\u2010<jats:bold>H5\u2010CA<\/jats:bold> and the cis\u2010<jats:bold>H5\u2010KA<\/jats:bold> was reversed by a kappa opioid receptor (KOR) antagonist. Naloxone and naltrindole were not effective. The cis\u2010isomers of CA conjugates and cis\u2010<jats:bold>H7\u2010KA<\/jats:bold> produced significantly stronger antinociceptive effects than their trans\u2010isomers. The cis\u2010<jats:bold>H5\u2010CA<\/jats:bold> antinociception was blocked by naloxone in the acute phase and by naloxone and KOR antagonists in the inflammatory phase of the formalin test. The antinociception of the KA conjugates was not abolished by opioid receptor blockade. None of the tested conjugates affected the thermal nociceptive threshold. The results of the docking analysis also suggest a model\u2010specific mechanism related to the activity of the cis\u2010isomers of CA and KA conjugates in relation to opioid receptors. Our findings pave the way for the further development of novel opioid\u2010related antiseizure and antinociceptive therapeutics.<\/jats:p>","DOI":"10.1002\/ddr.22236","type":"journal-article","created":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T04:09:30Z","timestamp":1721448570000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A novel cinnamic and caffeic acid\u2010conjugated peptide analogs with anticonvulsant and analgesic potency: Comparative analyses of <i>trans\/cis<\/i> isomers"],"prefix":"10.1002","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-5099","authenticated-orcid":false,"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 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