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The combination of scopolamine and <jats:sc>d<\/jats:sc>\u2010amphetamine is most effective in preventing severe motion sickness. However, this combination is not included in any present pharmacopoeia due to the abuse liability of <jats:sc>d<\/jats:sc>\u2010amphetamine. We wanted to find a combination to replace it for the treatment of severe motion sickness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We compared the efficacy of scopolamine, diphenhydramine, and granisetron (representing three classes of drugs) with different doses, and found that scopolamine was the most effective one. We also found scopolamine inhibited central nervous system at therapeutic doses and caused anxiety. Then, we combined it with different doses of psychostimulants (<jats:sc>d<\/jats:sc>\u2010amphetamine, modafinil, caffeine) to find the best combination for motion sickness. The efficacy of scopolamine with modafinil (1 + 10 mg\/kg) was equivalent to that of scopolamine with <jats:sc>d<\/jats:sc>\u2010amphetamine (1 + 1 mg\/kg); This combination also excited central nervous system and abolished the anxiety caused by scopolamine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The optimal dose ratio of scopolamine and modafinil is 1:10. This combination is beneficial for motion sickness and can abolish the side effects of scopolamine. So, it might be a good replacement of scopolamine and <jats:sc>d<\/jats:sc>\u2010amphetamine for severe motion sickness.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12566","type":"journal-article","created":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T05:04:26Z","timestamp":1462856666000},"page":"715-722","source":"Crossref","is-referenced-by-count":13,"title":["The Combination of Scopolamine and Psychostimulants for the Prevention of Severe Motion Sickness"],"prefix":"10.1111","volume":"22","author":[{"given":"Li\u2010Li","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu\u2010Hong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Sheng","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu\u2010Rui","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Minhang Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai\u2010Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,9]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1213","article-title":"Motion sickness: advances in pathogenesis, prediction, prevention, and treatment","volume":"77","author":"Shupak A","year":"2006","journal-title":"Aviat Space Environ Med"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12468"},{"key":"e_1_2_7_4_1","first-page":"192","article-title":"FPIN's clinical inquiries. treatment of motion sickness","volume":"86","author":"Sutton M","year":"2012","journal-title":"Am Fam Physician"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000163"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(98)00092-6"},{"key":"e_1_2_7_7_1","first-page":"44","article-title":"Neural mechanisms of motion sickness","volume":"48","author":"Takeda N","year":"2001","journal-title":"J Med Invest"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3357\/ASEM.3865.2014"},{"key":"e_1_2_7_9_1","first-page":"560","article-title":"Motion\u2010sickness medications for aircrew: impact on psychomotor performance","volume":"76","author":"Paul MA","year":"2005","journal-title":"Aviat Space Environ Med"},{"key":"e_1_2_7_10_1","first-page":"1215","article-title":"Mechanisms underlying the antimotion sickness effects of psychostimulants","volume":"58","author":"Kohl RL","year":"1987","journal-title":"Aviat Space Environ Med"},{"key":"e_1_2_7_11_1","first-page":"259","article-title":"Comparison of effectiveness of some antimotion sickness drugs using recommended and larger than recommended doses as tested in the slow rotation room","volume":"37","author":"Wood CD","year":"1966","journal-title":"Aerosp Med"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/00223989809599162"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/09595230801919460"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2015.03.009"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2014.01.001"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-6915(02)00096-0"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.112.007054"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-014-0537-1"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2010.08.004"},{"key":"e_1_2_7_20_1","first-page":"1","volume-title":"Newer antiemetics: final report update 1. 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