{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T07:34:18Z","timestamp":1774596858319,"version":"3.50.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Antazoline, a first-generation H\n                      <jats:sub>1<\/jats:sub>\n                      -antihistamine, has shown rapid and effective antiarrhythmic action, particularly in recent-onset paroxysmal atrial fibrillation. Despite clinical use in some countries, the underlying electrophysiological mechanisms remain incompletely understood, and concerns about potential proarrhythmic effects persist. Here, we aim to systematically characterize the ion channel interaction profile of antazoline and assess its molecular mode of action.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Electrophysiological measurements were performed using the two-electrode voltage clamp technique on 22 cardiac ion channels, expressed in\n                      <jats:italic>Xenopus laevis<\/jats:italic>\n                      oocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Antazoline strongly inhibited hERG (IC\n                      <jats:sub>50<\/jats:sub>\n                      end-pulse: 43.3 \u00b5M; peak-tail: 162.6\u00a0\u00b5M) and hKir3.1\/3.4 (IC\n                      <jats:sub>50<\/jats:sub>\n                      : 52.8\u00a0\u00b5M) in a concentration- and state-dependent manner. Block of hERG was attenuated by Y652A and F656A pore mutations, implicating classical aromatic binding residues. Positive rate dependence and open- and inactivated-state as well as partial closed-state inhibition were observed. In contrast, hK\n                      <jats:sub>2P<\/jats:sub>\n                      17.1 was significantly activated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Antazoline exhibits a distinct multichannel profile in a heterologous expression system, combining potent inhibition of hERG and hK\n                      <jats:sub>ir<\/jats:sub>\n                      3.1\/3.4 with activation of hK\n                      <jats:sub>2P<\/jats:sub>\n                      17.1. The combined modulation of these channels suggests a potential atrial-preferential electrophysiological profile, while hERG inhibition indicates a need for careful evaluation of ventricular repolarization safety.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1780526","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:36:57Z","timestamp":1774593417000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["From allergy to arrhythmia \u2013 electrophysiological basis for the antiarrhythmic properties of antazoline"],"prefix":"10.3389","volume":"17","author":[{"given":"Felix","family":"Wiedmann","sequence":"first","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Center Goettingen","place":["Goettingen, Germany"]},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Lower Saxony, University of Goettingen","place":["Goettingen, Germany"]},{"name":"Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital","place":["Heidelberg, Germany"]},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, University of Heidelberg","place":["Heidelberg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Prodanova","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital","place":["Heidelberg, Germany"]},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, University of Heidelberg","place":["Heidelberg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Kraft","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital","place":["Heidelberg, Germany"]},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, University of Heidelberg","place":["Heidelberg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederike Marie","family":"Weitkamp","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Center Goettingen","place":["Goettingen, Germany"]},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Lower Saxony, University of Goettingen","place":["Goettingen, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amelie","family":"Paasche","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital","place":["Heidelberg, Germany"]},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, University of Heidelberg","place":["Heidelberg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Goetz","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital","place":["Heidelberg, Germany"]},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, University of Heidelberg","place":["Heidelberg, Germany"]},{"name":"Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT)","place":["Karlsruhe, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constanze","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Center Goettingen","place":["Goettingen, Germany"]},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Lower Saxony, University of Goettingen","place":["Goettingen, Germany"]},{"name":"Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital","place":["Heidelberg, Germany"]},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, University of Heidelberg","place":["Heidelberg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/s0002-9394(14)74864-0","article-title":"Effects of topically applied occular decongestant and antihistamine","volume":"90","author":"Abelson","year":"1980","journal-title":"Am. 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