{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:22:18Z","timestamp":1793157738859,"version":"4.5.0"},"reference-count":61,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Heart Foundation PhD Scholarship"},{"name":"Endocrine Society of Australia Research Higher Degree Travel Scholarship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Primary aldosteronism (PA) is commonly caused by somatic mutations of CACNA1D encoding Cav1.3, one of the four L-type calcium channels. The over-the-counter drug, cinnarizine, fits the Cav1.3 crystal structure pore domain.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We hypothesized that Cav1.3 blockade by cinnarizine may achieve similar, or greater, reduction in aldosterone secretion than nonselective Cav1.2\/1.3 blockade by nifedipine.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Separate wells of angiotensin II\u2013stimulated HAC15 cells were treated with either cinnarizine (1-30\u2005\u03bcM) or nifedipine (1-100\u2005\u03bcM). Aldosterone concentrations were measured in culture medium; RNA extraction and quantitative polymerase chain reaction were performed to evaluate CYP11B2 expression. A prospective, open-label, crossover study was conducted of 15 adults with PA, treated with 2 weeks of cinnarizine 30\u2005mg 3 times a day or nifedipine extended release 60\u2005mg daily, separated by a 2-week washout. The hierarchical primary outcome was change in aldosterone-to-renin ratio (ARR), urinary tetrahydroaldosterone (THA), and plasma aldosterone concentration (PAC). Blood pressure change was a secondary outcome. Parametric analysis was undertaken on log-transformed data. (ClinicalTrials.gov: NCT05686993)<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Both drugs reduced aldosterone concentrations and CYP11B2 expression in vitro. Mean changes \u00b1 SEM in fold change of aldosterone concentrations and CYP11B2 were \u22120.47 \u00b1 0.05 and \u22120.56 \u00b1 0.07, respectively, with cinnarizine 30\u2005\u03bcM and \u22120.59 \u00b1 0.05 and \u22120.78 \u00b1 0.07 with nifedipine 100\u2005\u03bcM. In the clinical crossover trial, ARR was reduced by nifedipine but not cinnarizine (F = 3.25; P = .047); PAC rose with both drugs (F = 4.77; P = .013), but urinary THA was unchanged.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>A Cav1.3 ligand, cinnarizine, reduced aldosterone secretion from adrenocortical cells, but at maximum-soluble concentrations was less effective than the nonselective calcium blocker, nifedipine. At clinical doses, cinnarizine did not reduce plasma ARR in patients with PA, and, as in vitro, was inferior to nifedipine. The limited efficacy of high-dose nifedipine may be due to incomplete Cav1.3 blockade, or to a role for non\u2013L-type calcium channels in aldosterone secretion.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf081","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T09:21:35Z","timestamp":1741339295000},"page":"2752-2761","source":"Crossref","is-referenced-by-count":4,"title":["Evaluation of Aldosterone Suppression by Cinnarizine, a Putative Cav1.3 Inhibitor"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6649-032X","authenticated-orcid":false,"given":"Elisabeth","family":"Ng","sequence":"first","affiliation":[{"name":"Clinical Pharmacology & Precision Medicine, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square , London EC1M 6BQ ,","place":["UK"]},{"name":"Department of Endocrinology, St Bartholomew's Hospital, Barts Health , London EC1A 7BE ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Ni","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology & Precision Medicine, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square , London EC1M 6BQ ,","place":["UK"]},{"name":"Department of Endocrinology, St Bartholomew's Hospital, Barts Health , London EC1A 7BE ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Taylor","sequence":"additional","affiliation":[{"name":"Steroid Metabolome Analysis Core (SMAC), Institute of Metabolism and Systems Research, University of Birmingham , Birmingham B15 2TT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fozia","family":"Shaheen","sequence":"additional","affiliation":[{"name":"Steroid Metabolome Analysis Core (SMAC), Institute of Metabolism and Systems Research, University of Birmingham , Birmingham B15 2TT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Azizan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM) Medical Centre , Selangor 43600 ,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M","family":"Drake","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology & Precision Medicine, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square , London EC1M 6BQ ,","place":["UK"]},{"name":"Department of Endocrinology, St Bartholomew's Hospital, Barts Health , London EC1A 7BE ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8409-1082","authenticated-orcid":false,"given":"Morris J","family":"Brown","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology & Precision Medicine, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square , London EC1M 6BQ ,","place":["UK"]},{"name":"Department of Endocrinology, St Bartholomew's Hospital, Barts Health , London EC1A 7BE ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,2,10]]},"reference":[{"issue":"7","key":"2025091917013554400_dgaf081-B1","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1210\/jc.2016-1472","article-title":"Study heterogeneity and estimation of prevalence of primary aldosteronism: a systematic review and meta-regression analysis","volume":"101","author":"K\u00e4yser","year":"2016","journal-title":"J Clin Endocrinol 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