New findings in pharmacological effects induced by antihistamines: from PET studies to knock‐out mice
書誌事項
- 公開日
- 1999-07
- 権利情報
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- http://onlinelibrary.wiley.com/termsAndConditions#vor
- DOI
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- 10.1046/j.1365-2222.1999.00008.x-i1
- 公開者
- Wiley
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説明
<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>
収録刊行物
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- Clinical & Experimental Allergy
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Clinical & Experimental Allergy 29 (S3), 29-36, 1999-07
Wiley
