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Our research group has identified a new class of neuroactive peptides from the venom of a Brazilian social wasp, Polybia occidentalis, with the potential pharmacological profile to treat epilepsies. The study was divided into five phases: Phase 1 concerned the extraction, isolation and purification of Occidentalin-1202(n) from the crude venom, followed by the synthesis of an identical analogue peptide, named Occidentalin-1202(s). In Phase 2, we described the effects of both peptides in two acute models of epilepsy\u2014kainic acid and pentylenetetrazole-induced model of seizures\u2014and measured estimated ED50 and therapeutic index values, electroencephalographic studies and C-fos evaluation. Phase 3 was a compilation of advanced tests performed with Occidentalin-1202(s) only, reporting histopathological features and its performance in the pilocarpine-induced status epilepticus. After the determination of the antiepileptic activity of Occidentalin-1202(s), Phase 4 consisted of evaluating its potential adverse effects, after chronic administration, on motor coordination (Rotarod) and cognitive impairment (Morris water maze) tests. Finally, in Phase 5, we proposed a mechanism of action using computational models with kainate receptors. The new peptide was able to cross the blood\u2013brain barrier and showed potent antiseizure effects in acute (kainic acid and pentylenetetrazole) and chronic (temporal lobe epilepsy model induced by pilocarpine) models. Motor and cognitive behaviour were not adversely affected, and a potential neuroprotective effect was observed. Occidentalin-1202 can be a potent blocker of the kainate receptor, as assessed by computational analysis, preventing glutamate and kainic acid from binding to the receptor\u2019s active site. Occidentalin-1202 is a peptide with promising applicability to treat epilepsy and can be considered an interesting drug model for the development of new medicines.<\/jats:p>","DOI":"10.1093\/braincomms\/fcad016","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T15:59:58Z","timestamp":1676649598000},"source":"Crossref","is-referenced-by-count":8,"title":["A new class of peptides from wasp venom: a pathway to antiepileptic\/neuroprotective drugs"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6849-6001","authenticated-orcid":false,"given":"M\u00e1rcia Renata","family":"Mortari","sequence":"first","affiliation":[{"name":"Neuropharmacology Laboratory, Department of Physiological Sciences, Institute of Biological Sciences, University of Bras\u00edlia , Bras\u00edlia 71910-900 , Brazil"},{"name":"Neurobiology and Venoms Laboratory, Department of Biology, Faculty of Philosophy, Sciences and Literature of Ribeir\u00e3o Preto, University of S\u00e3o Paulo , S\u00e3o Paulo 14040-900 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra O S","family":"Cunha","sequence":"additional","affiliation":[{"name":"Neurobiology and Venoms Laboratory, Department of Biology, Faculty of Philosophy, Sciences and Literature of Ribeir\u00e3o Preto, University of S\u00e3o Paulo , S\u00e3o Paulo 14040-900 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian C","family":"dos Anjos","sequence":"additional","affiliation":[{"name":"Neuropharmacology Laboratory, Department of Physiological Sciences, Institute of Biological Sciences, University of Bras\u00edlia , Bras\u00edlia 71910-900 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique O","family":"Amaral","sequence":"additional","affiliation":[{"name":"Neuropharmacology Laboratory, Department of Physiological Sciences, Institute of Biological Sciences, University of Bras\u00edlia , Bras\u00edlia 71910-900 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Varela Torres","family":"Quintanilha","sequence":"additional","affiliation":[{"name":"Neuropharmacology Laboratory, Department of Physiological Sciences, Institute of Biological Sciences, University of Bras\u00edlia , Bras\u00edlia 71910-900 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica A","family":"Gelfuso","sequence":"additional","affiliation":[{"name":"Neuropharmacology Laboratory, Department of Physiological Sciences, Institute of Biological Sciences, University of Bras\u00edlia , Bras\u00edlia 71910-900 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Homem-de-Mello","sequence":"additional","affiliation":[{"name":"in Silico Toxicology Laboratory (inSiliTox), Department of Pharmacy, Health Sciences School, University of Brasilia , Brasilia 71910-900 , 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