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This study evaluated the indole alkaloids isocarapanaubine (indole alkaloid 1 [AIN1]) and 18\u2010\u03b2\u2010hydroxy\u20103\u2010epi\u2010\u03b1\u2010yohimbine (indole alkaloid 2 [AIN2]), extracted from <jats:italic>Rauvolfia ligustrina<\/jats:italic>, in adult zebrafish. Three doses (4, 12, and 20\u00a0mg\/kg) were tested, along with dimethyl sulfoxide (DMSO) 3% and Diazepam (4\u00a0mg\/kg) in toxicity, locomotion, and anxiolytic effect assays. AIN1 and AIN2 showed low toxicity (lethal dose capable of killing 50% of the animals &gt;20\u00a0mg\/kg) and reduced locomotor activity. Both exhibited anxiolytic effects, with AIN1 acting through the GABAergic system and AIN2 via the serotonergic pathway (5\u2010HT<jats:sub>3A<\/jats:sub>). Interactions with receptors were confirmed by molecular docking, and drug metabolism and pharmacokinetics studies indicated that AIN2 is promising in terms of permeability and safety in the central nervous system.<\/jats:p>","DOI":"10.1002\/cbdv.202500016","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T18:50:26Z","timestamp":1748976626000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anxiolytic Effects of Indole Alkaloids From <i>Rauvolfia ligustrina<\/i> in Adult Zebrafish: Involvement of the GABAergic and 5\u2010HT Systems"],"prefix":"10.1002","author":[{"given":"N\u00e1dia Aguiar Portela","family":"Pinheiro","sequence":"first","affiliation":[{"name":"Graduate Program in Natural Sciences State University of Cear\u00e1  Fortaleza Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana Carneiro","family":"Rom\u00e3o","sequence":"additional","affiliation":[{"name":"Graduate Program in Natural Sciences State University of Cear\u00e1  Fortaleza Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda Maria Barros","family":"Alves","sequence":"additional","affiliation":[{"name":"Graduate Program in Natural Sciences State University of Cear\u00e1  Fortaleza Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f4nia Maria Costa","family":"Siqueira","sequence":"additional","affiliation":[{"name":"Graduate Program in Natural Sciences State University of Cear\u00e1  Fortaleza Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane Eire Silva Alencar","family":"de Menezes","sequence":"additional","affiliation":[{"name":"Graduate Program in Natural Sciences State University of Cear\u00e1  Fortaleza Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel Silva","family":"Marinho","sequence":"additional","affiliation":[{"name":"Graduate Program in Natural Sciences State University of Cear\u00e1  Fortaleza Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rcia Machado","family":"Marinho","sequence":"additional","affiliation":[{"name":"Center for Exact Sciences and Technology State University of Vale do Acara\u00fa  Sobral Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herbert de Sousa","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Organic and Inorganic Chemistry Federal University of Cear\u00e1  Fortaleza Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreia Ferreira de Castro","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Biology, Environmental Biology, School of Sciences University of Minho  Braga Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ot\u00edlia Deusd\u00eania Loiola","family":"Pessoa","sequence":"additional","affiliation":[{"name":"Department of Organic and Inorganic Chemistry Federal University of Cear\u00e1  Fortaleza Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5527-164X","authenticated-orcid":false,"given":"H\u00e9lcio Silva","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Graduate Program in Natural Sciences State University of Cear\u00e1  Fortaleza Brazil"},{"name":"Center for Exact Sciences and Technology State University of Vale do Acara\u00fa  Sobral Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"WHO.Mental Disorders Accessed March 22 2025https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/mental\u2010disorders."},{"key":"e_1_2_9_3_1","unstructured":"WHO.World Mental Health Day 2023: Mental Health is a Basic Human Right Accessed March 22 2025https:\/\/www.emro.who.int\/media\/news\/world\u2010mental\u2010health\u2010day\u20102023\u2010mental\u2010health\u2010is\u2010a\u2010basic\u2010human\u2010right.html#:~:text=The%20global%20burden%20of%20mental prevalence%20among%20all%20WHO%20regions."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2020.05.009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.03.129"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.20510\/ukjpb\/6\/i3\/173546"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-40422007000400037"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12229-021-09262-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8836983"},{"key":"e_1_2_9_10_1","first-page":"979","article-title":"\u2018Indole Alkaloids of Rauvolfia Ligustrina and Their Anxiolytic Effects in Adult Zebrafish\u2019","volume":"89","author":"Sousa H. 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