{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361699995899496576.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1046/j.1365-2222.1999.00008.x-i1"}},{"identifier":{"@type":"URI","@value":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1365-2222.1999.00008.x-i1"}},{"identifier":{"@type":"URI","@value":"https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2222.1999.00008.x-i1"}},{"identifier":{"@type":"PMID","@value":"10444209"}}],"dc:title":[{"@value":"New findings in pharmacological effects induced by antihistamines: from PET studies to knock‐out mice"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Antihistamines are efficacious drugs to be used for the symptomatic relief of allergic diseases. The safety issue of antihistamines is of central importance because of their widespread use in current medical practice. To better understand the pharmacological effects of antihistamines on the central nervous system (CNS), we used two kinds of new methods, positron emission tomography (PET) and gene targeting regarding on histamine H<jats:sub>1</jats:sub>receptors. The histamine H<jats:sub>1</jats:sub>receptor occupancy was examined in young male volunteers with[<jats:sup>11</jats:sup>C]‐doxepin (a potent H<jats:sub>1</jats:sub>antagonist) after the oral or intravenous administration of antihistamines. In other studies, the cognitive performance was also measured tachistoscopically before and after taking antihistamines. The mutant mice lacking H<jats:sub>1</jats:sub>receptors were used in the behavioural and neurochemical experiments to re‐evaluate the role of H<jats:sub>1</jats:sub>receptors. The H<jats:sub>1</jats:sub>‐receptor occupancy in the human frontal cortex caused by antihistamines is significantly correlated with the reported values of incidence of sleepiness in clinical trials, and the occupancy is well proportional to the impaired cognitive performance. The behavioural studies of the H<jats:sub>1</jats:sub>‐receptor knock‐out mice confirmed the role of H<jats:sub>1</jats:sub>receptors in arousal, the sleep–wake cycle, locomotion, nociception and aggressive behaviour. The pharmacological effects induced by H<jats:sub>1</jats:sub>antagonism were re‐evaluated by the PET and gene‐targetting. Although any serious effects could not be observed in mice by the destruction of the H<jats:sub>1</jats:sub>‐receptor gene, the cognitive performance was impaired in humans after taking first generation antihistamines in recommended doses.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380290183773435904","@type":"Researcher","foaf:name":[{"@value":"K. Yanai"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995899496576","@type":"Researcher","foaf:name":[{"@value":"N. Okamura"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995899496577","@type":"Researcher","foaf:name":[{"@value":"M. Tagawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995899496579","@type":"Researcher","foaf:name":[{"@value":"M. Itoh"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995899496580","@type":"Researcher","foaf:name":[{"@value":"T. Watanabe"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"09547894"},{"@type":"EISSN","@value":"13652222"},{"@type":"PISSN","@value":"http://id.crossref.org/issn/09547894"}],"prism:publicationName":[{"@value":"Clinical & Experimental Allergy"}],"dc:publisher":[{"@value":"Wiley"}],"prism:publicationDate":"1999-07","prism:volume":"29","prism:number":"S3","prism:startingPage":"29","prism:endingPage":"36"},"reviewed":"false","dc:rights":["http://onlinelibrary.wiley.com/termsAndConditions#vor"],"url":[{"@id":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1365-2222.1999.00008.x-i1"},{"@id":"https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2222.1999.00008.x-i1"}],"createdAt":"2010-11-19","modifiedAt":"2025-02-28","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Male","dc:title":"Male"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Knockout","dc:title":"Mice, Knockout"},{"@id":"https://cir.nii.ac.jp/all?q=Pyrilamine","dc:title":"Pyrilamine"},{"@id":"https://cir.nii.ac.jp/all?q=Behavior,%20Animal","dc:title":"Behavior, Animal"},{"@id":"https://cir.nii.ac.jp/all?q=Histamine%20Antagonists","dc:title":"Histamine Antagonists"},{"@id":"https://cir.nii.ac.jp/all?q=Brain","dc:title":"Brain"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Doxepin","dc:title":"Doxepin"},{"@id":"https://cir.nii.ac.jp/all?q=Receptors,%20Histamine%20H1","dc:title":"Receptors, Histamine H1"},{"@id":"https://cir.nii.ac.jp/all?q=Cognition%20Disorders","dc:title":"Cognition Disorders"},{"@id":"https://cir.nii.ac.jp/all?q=Tomography,%20Emission-Computed","dc:title":"Tomography, Emission-Computed"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360002219657662080","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Positron emission tomography evaluation of sedative properties of antihistamines"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565166047934720","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Role of histamine H1-receptor on behavioral states and wake maintenance during deficiency of a brain activating system: A study using a knockout mouse model"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204272611200","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Towards Understanding Mechanisms of Drug Action and Functions of the Body on the Molecular Level. Studies on histamine with L-histidine decarboxylase, a histamine-forming enzyme, as a probe: from purification to gene knockout."},{"@language":"ja","@value":"薬の作用機序と生体機能の分子的理解に向けて　　ヒスタミンに関する研究　　ヒスチジン脱炭酸酵素の精製から欠損マウスまで"},{"@value":"ヒスタミンに関する研究:ヒスチジン脱炭酸酵素の精製から欠損マウスまで"},{"@language":"ja-Kana","@value":"ヒスタミン ニ カンスル ケンキュウ ヒスチジン ダツタンサン コウソ ノ セイセイ カラ ケッソン マウス マデ"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204628082432","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Identification of Human P450 Isoforms Involved in the Metabolism of the Antiallergic Drug, Oxatomide, and Its Inhibitory Effect on Enzyme Activity"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204632602240","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Evaluation of Efficacy and Sedative Profiles of H1 Antihistamines by Large-Scale Surveillance Using the Visual Analogue Scale (VAS)"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1046/j.1365-2222.1999.00008.x-i1"},{"@type":"OPENAIRE","@value":"doi_dedup___::9be94267034b523599afe339fb59be32"},{"@type":"CROSSREF","@value":"10.1248/bpb.27.684_references_DOI_D20GJEsH8xS19eoEYANqtG10OEg"},{"@type":"CROSSREF","@value":"10.2332/allergolint.o-07-525_references_DOI_D20GJEsH8xS19eoEYANqtG10OEg"},{"@type":"CROSSREF","@value":"10.1254/fpj.118.159_references_DOI_D20GJEsH8xS19eoEYANqtG10OEg"},{"@type":"CROSSREF","@value":"10.1517/14740338.2011.562889_references_DOI_D20GJEsH8xS19eoEYANqtG10OEg"},{"@type":"CROSSREF","@value":"10.1016/j.neuropharm.2015.12.014_references_DOI_D20GJEsH8xS19eoEYANqtG10OEg"}]}