Why are second-generation H1-antihistamines minimally sedating?
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.
Department of Biomedical Science, Iowa State University, Ames, IA, USA.
Yawen
Y
Hu
Department of Biomedical Science, Iowa State University, Ames, IA, USA.
Deidra E
DE
Sieck
Department of Biomedical Science, Iowa State University, Ames, IA, USA. Electronic address: whsu@iastate.edu.
Walter H
WH
Hsu
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D039563:Histamine H1 Antagonists, Non-Sedating / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006993:Hypnotics and Sedatives / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D039563:Histamine H1 Antagonists, Non-Sedating; D006993:Hypnotics and Sedatives
H(1)-antihistamine; MDR1; Minimally sedating; P-glycoprotein; Sedative effect