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The rotation stimulation and locomotor experiments were used to evaluate anti-motion sickness effects. The competitive affinity with [<jats:sup>3<\/jats:sup>H]-QNB and molecular docking were used for studying the interactions between the two isomers and mAChR. The stereoselective mechanism of isomers was investigated by incubation with rat liver microsomes, a protein binding assay and membrane permeability assay across a Caco-2 cell monolayer using a chiral column HPLC method. The results indicated that <jats:italic>S<\/jats:italic>-isomer was more effective against motion sickness and had not anxiogenic action at therapeutic doses. <jats:italic>S<\/jats:italic>-isomer has the higher affinity and activity for mAChR in cerebral cortex and acted as a competitive mAChR antagonist. The stereoselective elimination of <jats:italic>S<\/jats:italic>-isomer was primarily affected by CYP1B1 and 17A1 enzymes, resulting in a higher metabolic stability and slower elimination. Phencynonate <jats:italic>S<\/jats:italic> isomer, as a eutomer and central anticholinergic chiral drug, is a novel anti-motion sickness drug with higher efficacy and lower central side effect. Our data assisted the development of a novel drug and eventual use of <jats:italic>S<\/jats:italic>-isomer in clinical practice.<\/jats:p>","DOI":"10.1038\/s41598-018-38305-9","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T11:05:13Z","timestamp":1550055913000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Phencynonate S-isomer as a eutomer is a novel central anticholinergic drug for anti-motion sickness"],"prefix":"10.1038","volume":"9","author":[{"given":"Pingxiang","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuelin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhai","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianquan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Xue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,2,13]]},"reference":[{"key":"38305_CR1","first-page":"1213","volume":"77","author":"A Shupak","year":"2006","unstructured":"Shupak, A. & Gordon, C. 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