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Higenamine (HG) is a novel \u03b1\n                    <jats:sub>1<\/jats:sub>\n                    \u2010AR antagonist. In this study, we investigated the effects of HG in HEK293A cells transfected with \u03b1\n                    <jats:sub>1A<\/jats:sub>\n                    \u2010, \u03b1\n                    <jats:sub>1B<\/jats:sub>\n                    \u2010, and \u03b1\n                    <jats:sub>1D<\/jats:sub>\n                    \u2010AR in vitro, rat mesenteric artery ex vivo, Wistar\u2013Kyoto rats and spontaneously hypertensive rats in vivo. The radioligand binding assay showed that HG competitively inhibited the binding of [\n                    <jats:sup>3<\/jats:sup>\n                    H]\u2010prazosin to \u03b1\n                    <jats:sub>1<\/jats:sub>\n                    \u2010AR in a concentration\u2010dependent manner. The affinities (\n                    <jats:italic>p<\/jats:italic>\n                    Ki) of HG for the cloned \u03b1\n                    <jats:sub>1A<\/jats:sub>\n                    \u2010, \u03b1\n                    <jats:sub>1B<\/jats:sub>\n                    \u2010, and \u03b1\n                    <jats:sub>1D<\/jats:sub>\n                    \u2010AR were 6.57, 6.48, and 6.35, respectively, indicating that HG displayed no selectivity for the three \u03b1\n                    <jats:sub>1<\/jats:sub>\n                    \u2010AR subtypes. In in vitro studies, HG was able to blunt inositol monophosphate production. It also displayed an inhibitory effect on the influx and entry of calcium ions and phosphorylation of extracellular signal\u2010regulated kinase 1 and 2 induced by phenylephrine (PE). In ex vivo studies, PE caused a dose\u2010dependent inotropic response curve, and the pA\n                    <jats:sub>2<\/jats:sub>\n                    value for HG was 6.86\u00a0\u00b1\u00a00.29. In addition, the in vivo results showed that HG could decrease the blood pressure in normotension, spontaneous hypertension, and PE\u2010induced hypertension models. These results indicate that HG can directly bind to \u03b1\n                    <jats:sub>1<\/jats:sub>\n                    \u2010AR and it appears to be a novel antagonist for \u03b1\n                    <jats:sub>1<\/jats:sub>\n                    \u2010AR, which may contribute to its hypotensive effect.\n                  <\/jats:p>","DOI":"10.1002\/ptr.6261","type":"journal-article","created":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T22:08:33Z","timestamp":1547590113000},"page":"708-717","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Identification of higenamine as a novel \u03b1\n                    <sub>1<\/sub>\n                    \u2010adrenergic receptor antagonist"],"prefix":"10.1002","volume":"33","author":[{"given":"Nana","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory for Bioactive Substances and Functions of Natural Medicines; Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study; Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Qu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Bioactive Substances and Functions of Natural Medicines; Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study; Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjie","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Bioactive Substances and Functions of Natural Medicines; Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study; Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"},{"name":"School of Basic Medical Sciences Inner Mongolia Medical University, Jinshan Development District  Hohhot PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixiang","family":"Xue","sequence":"additional","affiliation":[{"name":"Medical Research Center Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haian","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Emory University School of Medicine  Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-5835","authenticated-orcid":false,"given":"Haibo","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Bioactive Substances and Functions of Natural Medicines; Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study; Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01649_1.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12863-017-0506-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.118.112573"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1768-322X.2004.tb01422.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2009.11.055"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2015.08.007"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-009-0174-4"},{"issue":"3","key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/S0095-4543(21)00423-1","article-title":"Compelled cesarean section. 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