EFFECT 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 D-4 (LTD(4)) 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 mu mol/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 close of 20 mg/kg. The drug inhibited LTD(4) release as well as histamine from lung fragments in actively sensitized guinea pigs. Loratadine inhibited not only Ca-45 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 charge in order parameter and phospholipase A(2) 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. Although loratadine had no effect on delayed type hypersensitivity response in mice, the drug was slightly effective in inhibiting active Arthus reaction in guinea pigs. These results indicate that the antiallergic effect of loratadine may be attributable to 1) its potent antihistaminic activity and 2) an inhibitory effect on histamine release. Loratadine can be considered to be useful for the treatment of some allergic diseases, especially allergic rhinitis and asthma, when the drug is employed in clinical use.