Verapamil, but not probenecid, co-administration can convert desloratadine to a sedating antihistamine in mice.
The possibility that non-sedating antihistamines could elicit sedation in mice due to drug-induced inhibition of brain PgP was evaluated by measuring the ability of desloratadine alone or in combination with verapamil to cause ataxia in mice. Also, the concentrations of desloratadine in plasma and in brain homogenates were measured by liquid chromatography-mass spectrometry. Relative to methylcellulose (control) treatment, verapamil plus desloratadine decreased rotarod performance of mice. Plasma concentrations of desloratadine appeared comparable in the mice treated with either desloratadine or verapamil plus desloratadine, however the rate of decline of desloratadine from brain tissue was slower in mice treated with verapamil plus desloratadine compared to mice treated with desloratadine only. These data suggest that inhibition of brain PgP can convert desloratadine to a sedating antihistamine in mice.
Department of Pharmacology, University of Toledo College of Pharmacy, Toledo, Ohio, USA.
Anand
A
Katta
Mugunthu
M
Dhananjeyan
Crystal
C
Bykowski
Paul
P
Erhardt
Miles
M
Hacker
Donald B
DB
White
Kenneth
K
Bachmann
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001259:Ataxia / Q000139:chemically induced; D001921:Brain / Q000378:metabolism; D002853:Chromatography, Liquid; D004347:Drug Interactions; D039563:Histamine H1 Antagonists, Non-Sedating / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D017336:Loratadine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D011339:Probenecid / Q000494:pharmacology; D014018:Tissue Distribution; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D039563:Histamine H1 Antagonists, Non-Sedating; D017336:Loratadine; D014700:Verapamil; C121345:desloratadine; D011339:Probenecid