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However, their involvement in the mammalian neurotoxicity remains unclear. Therefore, this study evaluated the systemic (neuro)toxicological action of MBG to understand its central effects, particularly those associated with seizure-inducing activity. Initially, physicochemical, pharmacokinetic, and drug-likeness profiles and molecular docking with receptors\/channels were investigated by in silico platforms. Next, the pro-convulsive action of MBG was investigated using pharmacological modulators for specific neurotransmission pathways and in vitro inhibitory activity of acetylcholinesterase was quantified. MBG has intestinal absorption and capacity to cross the blood\u2013brain barrier (BBB), binds strongly to plasma proteins, and acts as an inhibitory substrate for the CYP3A4 enzyme. It was classified as a drug-like molecule according to Lipinski\u2019s rule and ineligible according to the Lead-like and World Drug Index criteria. Molecular docking emphasized the interaction of MBG with ictogenesis-related targets, confirmed by reduction of in vivo seizures and death of pretreated animals with pharmacological blockers for dopamine D2 and glutamate NMDA receptors and Na\n                    <jats:sub>v<\/jats:sub>\n                    1.2 channels, mainly. It was shown that affinity of MBG for excitatory targets is essential for neuronal excitability and onset of seizures and that interaction with GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors is involved in bufadienolide-induced lethality. The findings also suggest that MBG-induced seizures may involve in silico binding to NMDA receptors and interactions with key excitatory (Na\n                    <jats:sub>v<\/jats:sub>\n                    1.2 channels and NMDA receptor) and inhibitory (GABA\n                    <jats:sub>A<\/jats:sub>\n                    and D2 receptors) neuronal targets, contributing to altered neuronal excitability. Notably, it is the first report that characterized MBG-induced seizures and proposes it as a promising chemical option to understand ictogenesis and mechanism(s) of new anticonvulsive agents.\n                  <\/jats:p>","DOI":"10.1007\/s00210-026-05462-y","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T02:27:11Z","timestamp":1779762431000},"page":"17693-17713","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Central toxic effects of an antitumoral bufadienolide: In silico targets and in vivo findings"],"prefix":"10.1007","volume":"399","author":[{"given":"Rayran Walter Ramos","family":"de Sousa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia Amanda Cardoso","family":"de Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"da Silva Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita de Cassia","family":"de Lima Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Railson Pereira","family":"Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layana Karine Farias","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco das Chagas Pereira","family":"de Andrade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson Nogueira","family":"Mendes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evaldo dos Santos","family":"Mon\u00e7\u00e3o Filho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Helena","family":"Chaves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo Magela Vieira","family":"Junior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domingos","family":"de Jesus Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalton","family":"Dittz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chistiane Mendes","family":"Feitosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Michel Pinheiro","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"5462_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112049","volume":"242","author":"S Abdelfatah","year":"2019","unstructured":"Abdelfatah S, Lu X, Schmeda-Hirschmann G et al (2019) Cytotoxicity and antimitotic activity of Rhinella schneideri and Rhinella marina venoms. 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Then, we fulfilled all Brazilian (\n                      Sociedade Brasileira de Ci\u00eancia em Animais de Laborat\u00f3rio\n                      \u2014SBCAL) and international guidelines for the care and use of animals in research (Directive 2010\/63\/EU of the European Parliament). Nulliparous female and no pregnant mice, 2\u20133\u00a0months-old and 25\u201330\u00a0g, were used. They were kept under standard conditions of light (12:12-h light\/dark cycle) and temperature (23\u2009\u00b1\u20092\u00a0\u00b0C) with free access to commercial rodent stock feed (Nutrilabor, Campinas, Brazil) and drinking water. Euthanasia was performed by a single overdose of sodium thiopental (150\u00a0mg\/kg i.p.).","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Clinical trial number.","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}