{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T09:54:14Z","timestamp":1781517254609,"version":"3.54.1"},"reference-count":50,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:00:00Z","timestamp":1781308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"CONAHCYT","doi-asserted-by":"publisher","award":["CBF2023-2024-2680"],"award-info":[{"award-number":["CBF2023-2024-2680"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Health, social, and ethical considerations highlight the need for new male contraceptives. Pimozide is an FDA approved drug known to block T-type calcium channels and which shares structural similarities with mibefradil, a proven antagonist of the CatSper channel. In this study, we examined the effect of pimozide on CatSper, a key target for non-hormonal male contraception. Molecular docking and molecular dynamics simulations were carried out to assess how pimozide binds within the channel pore, and binding energies were estimated using MM-GBSA. To determine its impact on sperm function, we evaluated hyperactivation, the acrosome reaction, and CatSper activity. Our computational analyses indicate that pimozide functions as a pore blocker of the CatSper channel. Experimental findings further support this, showing that pimozide inhibits CatSper activity, and impairs hyperactivation and the acrosome reaction in human spermatozoa. Overall, these results identify pimozide as a novel CatSper antagonist and propose a binding mode, offering a basis for the rational design of reversible, non-hormonal male contraceptives that target the CatSper channel.<\/jats:p>","DOI":"10.3390\/ijms27125357","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:57:58Z","timestamp":1781513878000},"page":"5357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pimozide Inhibits CatSper Activity, Impairs Hyperactivation and the Acrosome Reaction in Human Spermatozoa"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4703-237X","authenticated-orcid":false,"given":"Jorge Arturo","family":"Torres Ju\u00e1rez","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica Avanzada, Facultad de Medicina, Universidad Aut\u00f3noma de Quer\u00e9taro (UAQ), Santiago de Quer\u00e9taro 76010, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9040-3521","authenticated-orcid":false,"given":"Ana Gabriela","family":"Hern\u00e1ndez Puga","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica Avanzada, Facultad de Medicina, Universidad Aut\u00f3noma de Quer\u00e9taro (UAQ), Santiago de Quer\u00e9taro 76010, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0457-7558","authenticated-orcid":false,"given":"Esperanza","family":"Mata Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular y Desarrollo, Instituto de Fisiolog\u00eda Celular, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Lydia","family":"Trevi\u00f1o Santa Cruz","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica del Desarrollo y Fisiolog\u00eda Molecular, Instituto de Biotecnolog\u00eda (IBT), Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2671-2789","authenticated-orcid":false,"given":"Ana Alicia","family":"S\u00e1nchez Tusie","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica Avanzada, Facultad de Medicina, Universidad Aut\u00f3noma de Quer\u00e9taro (UAQ), Santiago de Quer\u00e9taro 76010, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tal, A. 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