{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:42:48Z","timestamp":1790358168234,"version":"4.1.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100030902","name":"Martin-Luther-Universit\u00e4t Halle-Wittenberg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100030902","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Dexmedetomidine is an approved drug that is chemically related to clonidine. Dexmedetomidine is used to induce sedation and anxiolysis. These therapeutic effects of dexmedetomidine are explained by its agonistic action on brain \u03b1\n                    <jats:sub>2<\/jats:sub>\n                    -adrenoceptors. We tested the hypothesis that dexmedetomidine like clonidine also stimulated human cardiac atrial H\n                    <jats:sub>2<\/jats:sub>\n                    -histamine-receptors. We noted that 10 \u00b5M dexmedetomidine increased force of contraction in electrically stimulated (1 Hz) human right atrial preparations (HAP, obtained during open heart surgery). These effects were increased by previously applied cilostamide and slightly attenuated by subsequently applied 10 \u00b5M cimetidine but greatly attenuated by 10 \u00b5M propranolol or when first 10 \u00b5M cocaine was given. After pre-stimulation with histamine, subsequently applied 1 \u00b5M dexmedetomidine reduced force of contraction in HAP. In left atrial preparations from mice with cardiac-specific overexpression of H\n                    <jats:sub>2<\/jats:sub>\n                    -histamine receptors (H\n                    <jats:sub>2<\/jats:sub>\n                    -TG), we noted a positive inotropic effect of 10 \u00b5M dexmedetomidine in the presence of 100 nM rolipram that was reversed by cimetidine. In left atrial preparations of wild-type mice, 10 \u00b5M dexmedetomidine increased force of contraction in the presence of rolipram which was reversed by subsequently applied 10 \u00b5M propranolol and attenuated by pretreatment with 10 \u00b5M cocaine. These data indicate a direct cardiac action of dexmedetomidine. Dexmedetomidine can probably, in principle, release endogenous cardiac noradrenaline. Thus, dexmedetomidine can act as a partial agonist at human cardiac H\n                    <jats:sub>2<\/jats:sub>\n                    -histamine receptors but its main effect in HAP is the release of endogenous \u03b2-adrenergic catecholamines.\n                  <\/jats:p>","DOI":"10.1007\/s00210-025-04192-x","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T06:18:42Z","timestamp":1748499522000},"page":"16149-16159","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Contractile effects of dexmedetomidine in the human heart"],"prefix":"10.1007","volume":"398","author":[{"given":"Joachim","family":"Neumann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Kirchhefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britt","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Gergs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"issue":"2","key":"4192_CR1","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1097\/00000542-199008000-00019","volume":"73","author":"VA Doze","year":"1990","unstructured":"Doze VA, Chen BX, Tinklenberg JA, Segal IS, Maze M (1990) Pertussis toxin and 4-aminopyridine differentially affect the hypnotic-anesthetic action of dexmedetomidine and pentobarbital. Anesthesiology. 73(2):304\u20137. https:\/\/doi.org\/10.1097\/00000542-199008000-00019","journal-title":"Anesthesiology."},{"key":"4192_CR2","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1097\/00000542-200008000-00016","volume":"93","author":"TJ Ebert","year":"2000","unstructured":"Ebert TJ, Hall JE, Barney JA et al (2000) The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 93:382\u2013394","journal-title":"Anesthesiology"},{"issue":"4","key":"4192_CR3","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/s00210-008-0371-y","volume":"379","author":"U Gergs","year":"2009","unstructured":"Gergs U, Neumann J, Simm A, Silber RE, Remmers FO, L\u00e4er S (2009) Phosphorylation of phospholamban and troponin I through 5-HT4 receptors in the isolated human atrium. Naunyn Schmiedebergs Arch Pharmacol. 379(4):349\u201359. https:\/\/doi.org\/10.1007\/s00210-008-0371-y","journal-title":"Naunyn Schmiedebergs Arch Pharmacol."},{"key":"4192_CR4","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1007\/s00210-013-0831-x","volume":"386","author":"U Gergs","year":"2013","unstructured":"Gergs U, B\u00f6ckler A, Ebelt H, Hauptmann S, Keller N, Otto V, P\u00f6nicke K, Schmitz W, Neumann J (2013) Human 5-HT4-receptor stimulation in atria of transgenic mice. Naunyn-Schmiedeberg\u2019s Arch Pharmacol 386:357\u2013367","journal-title":"Naunyn-Schmiedeberg\u2019s Arch Pharmacol"},{"key":"4192_CR5","doi-asserted-by":"publisher","first-page":"H1087","DOI":"10.1152\/ajpheart.00350.2017","volume":"313","author":"U Gergs","year":"2017","unstructured":"Gergs U, Jung F, Buchwalow IB, Hofmann B, Simm A, Treede H, Neumann J (2017) Pharmacological and physiological assessment of serotonin formation and degradation in isolated preparations from mouse and human hearts. Am J Physiol Heart Circ Physiol 313:H1087\u2013H1097","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"4192_CR6","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1124\/jpet.118.255711","volume":"369","author":"U Gergs","year":"2019","unstructured":"Gergs U, Bernhardt G, Buchwalow IB, Edler H, Fr\u00f6ba J, Keller M, Kirchhefer U, K\u00f6hler F, Mi\u00dflinger N, Wache H, Neumann J (2019) Initial characterization of transgenic mice overexpressing human histamine H2 receptors. J Pharmacol Exp Ther 369:129\u2013141","journal-title":"J Pharmacol Exp Ther"},{"key":"4192_CR7","doi-asserted-by":"publisher","unstructured":"Hamasaki J, Tsuneyoshi I, Katai R, Hidaka T, Boyle WA, Kanmura Y (2002) Dual alpha(2)-adrenergic agonist and alpha(1)-adrenergic antagonist actions of dexmedetomidine on human isolated endothelium-denuded gastroepiploic arteries. Anesth Analg 94(6):1434-40. table of contents. https:\/\/doi.org\/10.1097\/00000539-200206000-00010","DOI":"10.1097\/00000539-200206000-00010"},{"issue":"5","key":"4192_CR8","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1097\/00000542-199011000-00020","volume":"73","author":"PR Housmans","year":"1990","unstructured":"Housmans PR (1990) Effects of dexmedetomidine on contractility, relaxation, and intracellular calcium transients of isolated ventricular myocardium. Anesthesiology 73(5):919\u201322. https:\/\/doi.org\/10.1097\/00000542-199011000-00020","journal-title":"Anesthesiology"},{"issue":"3","key":"4192_CR9","doi-asserted-by":"publisher","first-page":"H769","DOI":"10.1152\/ajpheart.2000.278.3.H769","volume":"278","author":"L Li","year":"2000","unstructured":"Li L, Desantiago J, Chu G, Kranias EG, Bers DM (2000) Phosphorylation of phospholamban and troponin I in beta-adrenergic-induced acceleration of cardiac relaxation. Am J Physiol Heart Circ Physiol. 278(3):H769-79. https:\/\/doi.org\/10.1152\/ajpheart.2000.278.3.H769","journal-title":"Am J Physiol Heart Circ Physiol."},{"key":"4192_CR10","doi-asserted-by":"publisher","unstructured":"Masuki S, Dinenno FA, Joyner MJ, Eisenach JH (2005) Selective alpha2-adrenergic properties of dexmedetomidine over clonidine in the human forearm. J Appl Physiol (1985) 99(2):587-92. https:\/\/doi.org\/10.1152\/japplphysiol.00147.2005","DOI":"10.1152\/japplphysiol.00147.2005"},{"key":"4192_CR11","unstructured":"National Research Council (2011) Guide for the care and use of laboratory animals: eighth edition. The National Academies Press, Washington, DC"},{"issue":"10","key":"4192_CR12","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1006\/jmcc.1998.0760","volume":"30","author":"J Neumann","year":"1998","unstructured":"Neumann J, Boknik P, DePaoli-Roach AA, Field LJ, Rockman HA, Kobayashi YM, Kelley JS, Jones LR (1998) Targeted overexpression of phospholamban to mouse atrium depresses Ca2+ transport and contractility. J Mol Cell Cardiol. 30(10):1991\u20132002. https:\/\/doi.org\/10.1006\/jmcc.1998.0760","journal-title":"J Mol Cell Cardiol."},{"key":"4192_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.732842","author":"J Neumann","year":"2021","unstructured":"Neumann J, Kirchhefer U, Dhein S, Hofmann B, Gergs U (2021) The roles of cardiovascular H2-histamine-receptors under normal and pathophysiological conditions. Front Pharmacol. https:\/\/doi.org\/10.3389\/fphar.2021.732842","journal-title":"Front Pharmacol"},{"issue":"12","key":"4192_CR14","doi-asserted-by":"publisher","first-page":"2401","DOI":"10.1007\/s00210-021-02145-8","volume":"394","author":"J Neumann","year":"2021","unstructured":"Neumann J, Schwarzer D, Fehse C, Schwarz R, Marusakova M, Kirchhefer U, Hofmann B, Gergs U (2021) Functional interaction of H2-receptors and 5-HT4-receptors in atrial tissues isolated from double transgenic mice and from human patients. Naunyn-Schmiedeberg\u2019s Arch Pharmacol. 394(12):2401\u20132418. https:\/\/doi.org\/10.1007\/s00210-021-02145-8","journal-title":"Naunyn-Schmiedeberg\u2019s Arch Pharmacol."},{"key":"4192_CR15","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-023-02635-x52abcc56-dd8f-427e-a863-45914b75ab38","author":"J Neumann","year":"2023","unstructured":"Neumann J, Pockes S, Humphrys LJ, M\u00f6nnich D, Forster L, Kirchhefer U, Hofmann B, Ulrich Gergs U (2023a) Clonidine stimulates force of contraction via histamine H2-receptors in the human atrium. Naunyn-Schmiedeberg\u2019s Arch Pharmacol. https:\/\/doi.org\/10.1007\/s00210-023-02635-x52abcc56-dd8f-427e-a863-45914b75ab38","journal-title":"Naunyn-Schmiedeberg\u2019s Arch Pharmacol"},{"issue":"3","key":"4192_CR16","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1097\/FJC.0000000000001536","volume":"83","author":"J Neumann","year":"2023","unstructured":"Neumann J, Hu\u00dfler W, Hofmann B, Gergs U (2023b) Contractile effects of amphetamine, pseudoephedrine, nor-pseudoephedrine (cathine) and cathinone on atrial preparations of mice and humans. J Cardiovasc Pharmacol. 83(3):243\u2013250. https:\/\/doi.org\/10.1097\/FJC.0000000000001536","journal-title":"J Cardiovasc Pharmacol."},{"issue":"S3","key":"4192_CR17","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1124\/jpet.468.960520","volume":"389","author":"J Neumann","year":"2024","unstructured":"Neumann J, Hofmann B, Kirchhefer U, Gergs U (2024) Positive inotropic effects of dexmedetomidine in the human atrium. J Pharmacol Exp Ther 389(S3):468. https:\/\/doi.org\/10.1124\/jpet.468.960520","journal-title":"J Pharmacol Exp Ther"},{"issue":"2","key":"4192_CR18","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/0014-2999(91)90535-x","volume":"195","author":"JM Savola","year":"1991","unstructured":"Savola JM, Virtanen R (1991) Central alpha 2-adrenoceptors are highly stereoselective for dexmedetomidine, the dextro enantiomer of medetomidine. Eur J Pharmacol. 195(2):193\u20139. https:\/\/doi.org\/10.1016\/0014-2999(91)90535-x","journal-title":"Eur J Pharmacol."},{"issue":"3","key":"4192_CR19","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1016\/S0022-3565(25)20380-9","volume":"259","author":"DA Schwinn","year":"1991","unstructured":"Schwinn DA, Correa-Sales C, Page SO, Maze M (1991) Functional effects of activation of alpha-1 adrenoceptors by dexmedetomidine: in vivo and in vitro studies. J Pharmacol Exp Ther. 259(3):1147\u201352","journal-title":"J Pharmacol Exp Ther."},{"key":"4192_CR20","doi-asserted-by":"publisher","unstructured":"Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, Bin Kadiman S, McArthur CJ, Murray L, Reade MC, Seppelt IM, Takala J, Wise MP, Webb SA; ANZICS Clinical Trials Group and the SPICE III Investigators (2019) Early sedation with dexmedetomidine in critically ill patients. N Engl J Med 380(26):2506-2517. https:\/\/doi.org\/10.1056\/NEJMoa1904710","DOI":"10.1056\/NEJMoa1904710"},{"issue":"1\u20132","key":"4192_CR21","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/0014-2999(88)90744-3","volume":"150","author":"R Virtanen","year":"1988","unstructured":"Virtanen R, Savola JM, Saano V, Nyman L (1988) Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. Eur J Pharmacol. 150(1\u20132):9\u201314. https:\/\/doi.org\/10.1016\/0014-2999(88)90744-3","journal-title":"Eur J Pharmacol."},{"issue":"1","key":"4192_CR22","doi-asserted-by":"publisher","first-page":"54","DOI":"10.24920\/004294","volume":"39","author":"M Wang","year":"2024","unstructured":"Wang M, Che JX, Chen L, Song TT, Qu JT (2024) Effect of dexmedetomidine on intraoperative hemodynamics and blood loss in patients undergoing spine surgery: a systematic review and meta-analysis. Chin Med Sci J. 39(1):54\u201368. https:\/\/doi.org\/10.24920\/004294","journal-title":"Chin Med Sci J."},{"issue":"8","key":"4192_CR23","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1007\/s40262-017-0507-7","volume":"56","author":"MAS Weerink","year":"2017","unstructured":"Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P (2017) Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine. Clin Pharmacokinet. 56(8):893\u2013913. https:\/\/doi.org\/10.1007\/s40262-017-0507-7","journal-title":"Clin Pharmacokinet."},{"issue":"5","key":"4192_CR24","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1053\/j.jvca.2006.11.005","volume":"21","author":"O Yildiz","year":"2007","unstructured":"Yildiz O, Ulusoy HB, Seyrek M, Gul H, Yildirim V (2007) Dexmedetomidine produces dual alpha2-adrenergic agonist and alpha1-adrenergic antagonist actions on human isolated internal mammary artery. J Cardiothorac Vasc Anesth. 21(5):696\u2013700. https:\/\/doi.org\/10.1053\/j.jvca.2006.11.005","journal-title":"J Cardiothorac Vasc Anesth."}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-04192-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-025-04192-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-04192-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T11:14:56Z","timestamp":1761304496000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-025-04192-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,29]]},"references-count":24,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["4192"],"URL":"https:\/\/doi.org\/10.1007\/s00210-025-04192-x","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,29]]},"assertion":[{"value":"23 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Animals\n                      : The investigation conformed to the Guide for the Care and Use of Laboratory Animals as published by the National Research Council (\n                      \n                      ). The animals were handled and maintained according to the approved protocols of the Animal Welfare Committee of the University of Halle-Wittenberg, Halle, Germany (#TS 10 -\u200924).\n                      Humans\n                      : This study in patients complies with the Declaration of Helsinki and has been approved by the local ethics committee (#hm-b\u00fc 04.08.2005).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed written consent was obtained from all patients included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors declare that they have seen and approved the submitted version of this manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}