{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T20:25:35Z","timestamp":1750451135286,"version":"3.40.5"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To characterise the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of oxathridine, a first\u2010in\u2010class histamine\u20103 receptor partialagonist, in healthy male volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A randomised, double\u2010blind, placebo\u2010controlled study including the NeuroCart, consisting of a battery of drug sensitive neurophysiological tests, was performed. Oxathridine was administered orally as an aqueous solution. After dosing, safety and NeuroCart tests (adaptive tracking [AT], body sway [BS], saccadic peak velocity [SPV], smooth pursuit [SP] eye movements, VAS according to Bond and Lader, VAS according to Bowdle [VAS B&amp;L, Bowdle], pharmaco\u2010electroencephalogram [pEEG], Sustained Attention to Response Task [SART]) were performed at set times.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>\u00a0\u00a0Forty volunteers completed the study. Given doses were: 0.5, 2.5, 5, 0.25 and 1.5 mg. At 5 mg, unacceptable and unanticipated adverse events (AEs) of (orthostatic) hypotension and pseudo\u2010hallucinations were reported. Statistically significant effects ([CI]; <jats:italic>p<\/jats:italic>\u2010value) of 2.5 mg and 5 mg oxathridine were observed on AT ([\u22128.28, \u22121.60]; <jats:italic>p<\/jats:italic> = 0.0048), ([\u22128.10, \u22121.51]; <jats:italic>p<\/jats:italic> = 0.00530), BS ([0.6, 80.2]; <jats:italic>p<\/jats:italic> = 0.0455), ([5.9, 93.1]; <jats:italic>p<\/jats:italic> = 0.0205) and SPV ([\u221259.0, \u221215.9]; <jats:italic>p<\/jats:italic> = 0.0011), ([\u221243.9, \u22121.09]; <jats:italic>p<\/jats:italic> = 0.0399), respectively. Oxathridine 5 mg significantly increased all three VAS Bowdle subscale scores; VAS external ([0.183, 0.476]; <jats:italic>p<\/jats:italic> = &lt;.0001), VAS internal ([0.127, 0.370]; <jats:italic>p<\/jats:italic> = 0.0001) and VAS feeling high ([0.263, 0.887]; <jats:italic>p<\/jats:italic> = 0.0006).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>NeuroCart tests indicated central nervous system (CNS) depressant effects. Oxathridine also unexpectedly caused pseudohallucinations. Although this led to the decision to stop further development of oxathridine, these observations suggest that the H3R system could be an interesting new target for the development of novel antipsychotics.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15910","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T11:08:19Z","timestamp":1695121699000},"page":"321-335","source":"Crossref","is-referenced-by-count":1,"title":["Administration of oxathridine, a first\u2010in\u2010class histamine\u20103 receptor partial agonist in healthy male volunteers: Central nervous system depression and pseudo\u2010hallucinations"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5804-0708","authenticated-orcid":false,"given":"Francis M.","family":"Dijkstra","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research  Leiden the Netherlands"},{"name":"Leiden University Medical Center  Leiden ZA the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5604-0157","authenticated-orcid":false,"given":"Rob G. 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