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This biogenic compound acts through the activation of seven 5\u2010HT receptors (5\u2010HT<jats:sub>1\u20107<\/jats:sub>Rs). The 5\u2010HT<jats:sub>3<\/jats:sub>R is a ligand\u2010gated ion channel belonging to the Cys\u2010loop receptor family. There is a wide variety of 5\u2010HT<jats:sub>3<\/jats:sub>R modulators, but only receptor antagonists (known as setrons) have been used clinically for chemotherapy\u2010induced nausea and vomiting and irritable bowel syndrome treatment. However, since the discovery of the setrons in the mid\u20101980s, a large number of studies have been published exploring new potential applications due their potency in the CNS and mild side effects. The results of these studies have revealed new potential applications, including the treatment of neuropsychiatric disorders such as schizophrenia, depression, anxiety, and drug abuse. In this review, we provide information related to therapeutic potential of 5\u2010HT<jats:sub>3<\/jats:sub>R antagonists on GI and neuropsychiatric disorders. The major attention is paid to the structure, function, and pharmacology of novel 5\u2010HT<jats:sub>3<\/jats:sub>R modulators developed over the past 10 years.<\/jats:p>","DOI":"10.1002\/med.21666","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T05:25:03Z","timestamp":1583126703000},"page":"1593-1678","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Recent advances with 5\u2010HT<sub>3<\/sub> modulators for neuropsychiatric and gastrointestinal disorders"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0842-7343","authenticated-orcid":false,"given":"Radomir","family":"Juza","sequence":"first","affiliation":[{"name":"National Institute of Mental Health  Klecany Czech Republic"},{"name":"Department of Chemistry University of Hradec Kralove  Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1671-1590","authenticated-orcid":false,"given":"Premysl","family":"Vlcek","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health  Klecany Czech Republic"},{"name":"Third Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9986-5017","authenticated-orcid":false,"given":"Eva","family":"Mezeiova","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre University Hospital Hradec Kralove  Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7504-4062","authenticated-orcid":false,"given":"Kamil","family":"Musilek","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Hradec Kralove  Hradec Kralove Czech Republic"},{"name":"Biomedical Research Centre University Hospital Hradec Kralove  Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6376-8701","authenticated-orcid":false,"given":"Ondrej","family":"Soukup","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre University Hospital Hradec Kralove  Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6977-7596","authenticated-orcid":false,"given":"Jan","family":"Korabecny","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health  Klecany Czech Republic"},{"name":"Biomedical Research Centre University Hospital Hradec Kralove  Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1078197"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(86)80278-9"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.11.002"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1256"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-003-1100-5"},{"key":"e_1_2_5_7_1","first-page":"20225","article-title":"Biogenic amine neurotransmitter transporters: just when you thought you knew them","volume":"20","author":"Blakely RD","year":"2005","journal-title":"Physiol Bethesda Md"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781118385777"},{"key":"e_1_2_5_9_1","first-page":"21203","article-title":"The degradation of serotonin: role of MAO","author":"Bortolato M","year":"2010","journal-title":"Handb Behav Neurosci"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02147990"},{"key":"e_1_2_5_11_1","first-page":"51","volume-title":"Handbook of the Behavioral Neurobiology of Serotonin","author":"Hornung J\u2010P"},{"key":"e_1_2_5_12_1","first-page":"12323","article-title":"Two kinds of tryptamin receptor","author":"Gaddum JH","year":"1957","journal-title":"Br J Pharmacol Chemother"},{"issue":"2","key":"e_1_2_5_13_1","first-page":"157","article-title":"International union of pharmacology classification of receptors for 5\u2010hydroxytryptamine (Serotonin)","volume":"46","author":"Hoyer D","year":"1994","journal-title":"Pharmacol Rev"},{"key":"e_1_2_5_14_1","first-page":"1615","article-title":"5\u2010HT3 receptors mediate rapid responses in cultured hippocampus and a clonal cell line","author":"L. 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