Why are second-generation H₁-antihistamines minimally sedating?

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• 作者：Yawen Hu ; Deidra E. Sieck ; Walter H. Hsu ; ^{whsu@iastate.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：H1-antihistamine ; P-glycoprotein ; MDR1 ; Sedative effect ; Minimally sedating
• 刊名：European Journal of Pharmacology
• 出版年：2015
• 出版时间：15 October 2015
• 年：2015
• 卷：765
• 期：Complete
• 页码：100-106
• 全文大小：536 K

文摘

H₁-antihistamines are widely used in treating allergic disorders, e.g., conjunctivitis, urticaria, dermatitis and asthma. The first-generation H₁-antihistamines have a much greater sedative effect than the second-generation H₁-antihistamines. Researchers could not offer a satisfactory explanations until late 1990s when studies showed that second-generation H₁-antihistamines were substrates of P-glycoprotein. P-glycoprotein, expressed in the blood–brain barrier, acts as an efflux pump to decrease the concentration of H₁-antihistamines in the brain, which minimizes drug effects on the central nervous system and results in less sedation. P-glycoprotein is found in the apical side of the epithelium. It consists of transmembrane domains that bind substrates/drugs and nucleotide-binding domains that bind and hydrolyze ATP to generate energy for the drug efflux. This review mainly discusses interactions between P-glycoprotein and commonly used second-generation H₁-antihistamines. In addition, it describes other possible determining factors of minimal sedating properties of second-generation H₁-antihistamines.