Effect of loratadine on immediate and delayed type hypersensitivity reactions

Loratadine (CAS 79794-75-5) was effective in inhibiting the contractions of the ileum induced by histamine in guinea pigs. The drug also caused an anti-acetylcholine, anti-serotonin and anti-leukotriene D4 (LTD4) effect. In addition, loratadine inhibited the synthesis of leukotrienes more potently than ketotifen. On the other hand, in in vitro studies of histamine release from rat peritoneal mast cells induced by compound 48/80 or lung fragments in actively sensitized guinea, pigs, loratadine elicited a significant inhibition at a concentration of 5 mumol/l. In ex vivo studies, the drug inhibited histamine release from lung fragments induced by concanavalin A, and significant effect lasted for 24 h when the drug was administered at a dose of 20 mg/kg. The drug inhibited LTD4 release as well as histamine from lung fragments in actively sensitized guinea pigs. Loratadine inhibited not only 45Ca uptake into the rat peritoneal mast cells but also Ca2+ release from the intracellular Ca store induced by compound 48/80 or A23187. Loratadine increased cAMP content in rat lung preparation while decreasing cGMP content. Loratadine caused no significant change in order parameter and phospholipase A2 activity. The drug was more potent than ketotifen and terfenadine in inhibiting antigen-induced increase in airway resistance in guinea pigs. In addition, the effect of loratadine on airway resistance was sustained for 12 h. Loratadine inhibited an increase in dye leakage into the nasal cavity in rats.(ABSTRACT TRUNCATED AT 250 WORDS)