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This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this double\u2010blind, placebo\u2010controlled, three\u2010way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5\u00a0mg and diphenhydramine 50\u00a0mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two\u2010back, and Stroop). Regional cerebral glucose consumption changes were measured using positron emission tomography with [<jats:sup>18<\/jats:sup>F]fluorodeoxyglucose. Regional hemodynamic responses were measured using near\u2010infrared spectroscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Energy consumption in prefrontal regions was significantly increased after antihistamine administration, especially diphenhydramine, whereas prefrontal hemodynamic responses, evaluated with oxygenated hemoglobin levels, were significantly lower with diphenhydramine treatment. Stroop test accuracy was significantly impaired by diphenhydramine, but not by levocetirizine. There was no significant difference in subjective sleepiness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Physiological \u201ccoupling\u201d between metabolism and perfusion in the healthy human brain may not be maintained under pharmacological influence due to antihistamines. This uncoupling may be caused by a combination of increased energy demands in the prefrontal regions and suppression of vascular permeability in brain capillaries after antihistamine treatment. Further research is needed to validate this hypothesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hup.2655","type":"journal-article","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T10:30:06Z","timestamp":1521109806000},"source":"Crossref","is-referenced-by-count":1,"title":["Effects of levocetirizine and diphenhydramine on regional glucose metabolic changes and hemodynamic responses in the human prefrontal cortex during cognitive tasks"],"prefix":"10.1002","volume":"33","author":[{"given":"Asuka","family":"Kikuchi","sequence":"first","affiliation":[{"name":"Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center Tohoku University  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fairuz Binti Mohammadi","family":"Nasir","sequence":"additional","affiliation":[{"name":"Division of Radiation Safety, Cyclotron and Radioisotope Center Tohoku University  Sendai 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