Why are second-generation H-1-antihistamines minimally sedating?

作者：Hu Yawen; Sieck Deidra E; Hsu Walter H^*

来源：European Journal of Pharmacology, 2015, 765: 100-106.

DOI：10.1016/j.ejphar.2015.08.016

• H-1-antihistamine
• P-glycoprotein
• MDR1
• Sedative effect
• Minimally sedating

H-1-antihistamines are widely used in treating allergic disorders, e.g., conjunctivitis, urticaria, dermatitis and asthma. The first-generation H-1-antihistamines have a much greater sedative effect than the second-generation H-1-antihistamines. Researchers could not offer a satisfactory explanations until late 1990s when studies showed that second-generation H-1-antihistamines were substrates of P-glycoprotein. P-glycoprotein, expressed in the blood-brain barrier, acts as an efflux pump to decrease the concentration of H-1-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 H-1-antihistamines. In addition, it describes other possible determining factors of minimal sedating properties of second-generation H-1-antihistamines.

• 出版日期2015-10-15