{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T21:44:14Z","timestamp":1780523054152,"version":"3.54.1"},"reference-count":135,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T00:00:00Z","timestamp":1738454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union (Next Generation EU)","award":["20228XNEC4"],"award-info":[{"award-number":["20228XNEC4"]}]},{"name":"European Union (Next Generation EU)","award":["RF-2021-123730.36"],"award-info":[{"award-number":["RF-2021-123730.36"]}]},{"name":"Italian Ministry of Health","award":["20228XNEC4"],"award-info":[{"award-number":["20228XNEC4"]}]},{"name":"Italian Ministry of Health","award":["RF-2021-123730.36"],"award-info":[{"award-number":["RF-2021-123730.36"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Trilostane is a drug able to block the synthesis of progesterone from pregnenolone, dependent on the enzyme 3\u03b2-hydroxysteroid dehydrogenase\/\u03945\u22124 isomerase. As a consequence of this effect, it is used to treat endocrinological diseases such as Cushing\u2019s syndrome, especially in dogs. Because of the modulatory effects of trilostane on the hypothalamic\u2013pituitary\u2013adrenal axis, trilostane administration causes an increase in brain levels of neurosteroids with anticonvulsant properties, as in the case of allopregnanolone. Allopregnanolone is also of interest in curing depression, suggesting that trilostane might represent a tool to address neurological and psychiatric disorders. In this review, we investigated the historical development of this drug and its current use, mechanisms, and possible developments. By searching the literature from 1978 to 2025, we identified 101 papers describing studies with trilostane. Precisely, 55 were about dogs and trilostane, 3 were on cats, and 23 were with other animals. Some studies (15) were also designed with human patients. The main disease treatment with trilostane was hyperadrenocorticism. However, we also found two preclinical papers on trilostane\u2019s potential use in psychiatric diseases and three on trilostane\u2019s potential use in neurological disorders. Moreover, few clinical and preclinical studies suggested the involvement of neurosteroids modulated by trilostane in different neurological disorders, thus opening a possible new perspective for the use of this drug.<\/jats:p>","DOI":"10.3390\/ani15030415","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T08:47:57Z","timestamp":1738572477000},"page":"415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Trilostane: Beyond Cushing\u2019s Syndrome"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6079-6062","authenticated-orcid":false,"given":"Ali R.","family":"Olaimat","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Epilepsy, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Health Innovative Products and Technologies (HIP-TECH) Ph.D. Program, Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6171-2197","authenticated-orcid":false,"given":"Parastoo","family":"Jafarzadehbalagafsheh","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Epilepsy, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5189-1008","authenticated-orcid":false,"given":"Mohammad","family":"Gol","sequence":"additional","affiliation":[{"name":"Radiology Department, South Tyneside and Sunderland NHS Foundation Trust, Sunderland SR4 7TP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Maria","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Epilepsy, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7130-2511","authenticated-orcid":false,"given":"Giuseppe","family":"Biagini","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Epilepsy, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Lucchi","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Epilepsy, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1021\/jm00299a034","article-title":"Steroidal heterocycles. 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