Effects of AHR-5333, a new potential antiallergy compound, in in vivo models of immediate hypersensitivity.
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 X), ketotifen (approximately 3 X), oxatomide (approximately 5 X), albuterol (6 X) and aminophylline (approximately 50 X) in a passive, foot anaphylaxis model in rats and more potent than diphenhydramine (approximately 237 X), oxatomide (approximately 5.6 X) and theophylline (approximately 295 X) 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.
D000284:Administration, Oral; D000707:Anaphylaxis / Q000139:chemically induced; D000818:Animals; D000947:Antigens, Helminth / Q000494:pharmacology; D001200:Ascaris / Q000276:immunology; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006969:Hypersensitivity, Immediate / Q000188:drug therapy*; D008252:Macaca fascicularis; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D012882:Skin Tests
D000947:Antigens, Helminth; D006634:Histamine H1 Antagonists; D010880:Piperidines; C055541:AHR 5333