Circadian Time-Dependent Differences in Murine Tolerance to the Antihistaminic Agent Loratadine

• Published in: Chronobiology international 2005-01, Vol.22 (3), p.499-514
• Main Authors: Dridi, Dorra, Boughattas, Naceur A., Aouam, Karim, Reinberg, Alain, Ben Attia, Mossadok
• Format: Article
• Language: English
• Subjects: Animals; Body Temperature; Body Weight; Brain - drug effects; Chronotoxicology; Circadian Rhythm; Circadian Rhythm - physiology; Core Body Temperature; Drug Tolerance - physiology; Histamine H1 Antagonists, Non-Sedating - metabolism; Histamine H1 Antagonists, Non-Sedating - toxicity; Loratadine; Loratadine - metabolism; Loratadine - toxicity; Male; Mice; Neurotoxicity; Neurotoxins - metabolism; Survival Rate; Time Factors
• ISSN: 0742-0528; 1525-6073
• DOI: 10.1081/CBI-200062369

Loratadine is a second-generation histamine H1-receptor antagonist used in the treatment of allergic diseases. The aim of the study was to assess whether lethal toxicity and motor incoordination (neurotoxicity) of loratadine is circadian rhythm-dependent. A total of 210 male Swiss mice, aged 10 wk, were synchronized for 3 wk to 12 h light (rest span) 12 h dark (activity span). The drug was administered per os. The choice of the sublethal (TD50=82 mg kg body weight) and the lethal (LD50=4 g kg body weight) dosage was based on preliminary studies. Each of these two doses was administered to comparable groups of animals at six different circadian time points (1, 5, 9, 13, 17, and 21 Hours After Light Onset [HALO]). The survival duration was dosing time-dependent (χ2=16.96; p