ABSTRACT-To clarify the antiallergic effect and antiallergic mechanism of -1-piperazinyl]butyl]-3-(6-methyl-3-pyridyl)acrylamide) in monkeys, its effects on the Prausnitz-Kustner (P-K) reaction, the histamine skin reaction and leukotriene production were examined. In contrast to ketotifen and mepyramine, AL-3264 inhibited the P-K reaction, which is mainly mediated by leukotriene and histamine, more clearly than the skin reaction evoked by histamine alone. AL-3264 also inhibited the leukotriene (LT) production in the broncho-alveolar cells, suggesting that the inhibition of LT production actually contributes to the antiallergic effect of AL-3264.Keywords: AL-3264, Prausnitz-Kustner reaction, Monkey(AL-3264) is a new antiallergic agent that possesses a 5-lipoxygenase (5-LO) inhibiting property together with the abilities to block histamine HI-receptors and inhibit histamine release (1), but has very little sedative effect (2). The metabolism of AL-3264 in humans has also been assessed to be similar to that in monkeys, but not in rats.The monkey is thought to be a good experimental animal in which to develop allergic reactions, i.e., asthma, cedar pollinosis and the Prausnitz-Kustner (P-K) reaction (3 -5), because its mast cells and basophils can be passively sensitized with human IgE antibody (6, 7). We recently revealed that the P-K reaction in monkeys is mediated by leukotriene (LT) and histamine, similar to the mediation of human allergic diseases, and proposed that it is useful for the evaluation of antiallergic drugs (unpublished data, I. Yakuo and H. Nakamura).Some antiallergic drugs with multiple mechanisms of action have been developed, but these in vivo mechanisms of action have hardly been compared at the same time and at the effective dose. To assess the antiallergic effect and antiallergic mechanism of AL-3264 in monkeys, the effect of AL-3264 on the P-K reaction was compared with that on the histamine skin reaction in the same monkeys.Furthermore, its effect on LT production was examined using the broncho-alveolar cells of monkeys pretreated with AL-3264. Broncho-alveolar lavage is a useful method for the collection of proinflammatory cells and for the diagnosis or treatment of respiratory diseases. The method that is generally used in clinical studies is applied to experimental animals such as monkeys. Young adult cynomolgus monkeys (Japan SLC, Inc., Hamamatsu) were used for the experiments at an interval of more than a month. The P-K reaction was performed as follows: Forearm skin sites of monkeys (female, 2.5-4 kg) were sensitized with an intradermal injection (20 p1/site) of 5 times-diluted serum from an asthmatic patient. Two days later, the monkeys were challenged with dust mite antigen extract by an intradermal injection (0.2 pg/20 pl/site) into the 6 sensitized skin sites. In the same monkeys, the histamine skin reaction was also induced by an intradermal injection of histamine solution (0.2 pg/20 pl/site) into 5 unsensitized forearm skin sites. After 20 min (antigen injection) or 10 min (hist...

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