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  • 1
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract AHR-13268D (4-[3-[4-[Bis(4-flurophenyl)hydroxymethyl]-1-piperidinyl]propoxy]benzoic acid, sodium salt) is a potent, long-acting water soluble, antiallergic and antihistaminic agent. AHR-13268D protects sensitive guinea pigs from collapse induced by aerosolized antigen; 1, 5, and 24 h ED50s in the test were 0.27, 0.25, 0.93 mg/kg, PO, respectively. AHR-13268D was also active when given as an aerosol, the 1 h ED50=0.29%. In the rat passivefoot anaphylaxis test, AHR-13268D was slightly more active (1.55 times) than AHR-5333B when given orally 1 h prior to challenge and equipotent to cromolyn when given intravenously immediately prior to challenge. AHR-13268D displayed potent, long-acting antihistaminic activity in naive guinea pigs; the 1, 5, and 24 h oral ED50s being in the range of 0.3 mg/kg. AHR-13268D (10 to 20 mg/kg, PO) attenuated the skin responses to ascaris antigen in sensitive dogs and did not alter the EEG pattern or sleep/wake patterns of cats at doses in vast excess of its antihistaminic activity.In vitro, AHR-13268D was a potent inhibitor of histamine release from rat peritoneal mast cells (IC50=0.51 nM) and was as potent as the reference 5-LO inhibitor phenidone in inhibiting antigen-induced contractions of guinea pig ileum in the presence of pyrilamine, atropine, and imidazole (IC50∼300 μM). AHR-13268B was bioavailable (∼88%) from capsules or from oral solutions.
    Type of Medium: Electronic Resource
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