Effects of AHR-5333, a New Potential Antiallergy Compound, in in vivo Models of Immediate Hypersensitivity

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Abstract
AHR-5333 [1-[4-[3-[4-[bis(4-fluorophenyl)hydroxymethyl]-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone] possessed potent, long-acting activity in rat and guinea pig in vivo models of immediate hypersensitivity. AHR-5333 was more potent than azatadine (2×), ketotifen (∼3 ×), oxatomide (∼5 ×), albuterol (6 ×) and aminophylline (∼ 50 ×) in a passive, foot anaphylaxis model in rats and more potent than diphenhydramine (∼237 ×), oxatomide (∼5.6 ×) and theophylline (∼295 ×) in guinea pigs challenged with aerosolized antigen. A long duration of action was noted after oral dosing of guinea pigs (24 h PD50, 0.78 mg/kg). Administration by aerosol (1%) to sensitized, spontaneously breathing, conscious guinea pigs protected against antigen-induced anaphylactic collapse; this protection persisted through 8 h. When administered prior to antigen challenge, AHR-5333 (10 mg/kg, p.o.) effectively inhibited ascaris antigen-induced skin hypersensitivity reactions in both dogs and cynomolgus monkeys.