AHR-14310C(5-[2-[4-[bis(4-fluorophenyl)hydroxymethyl- 1-piperidinyl]ethyl]-3-methyl]-
2-oxazolidinone ethanedioate, hydrochloride
salt) displays potent and long-acting antihistaminic activity in guinea pigs and in dog and guinea pig models of
immediate hypersensitivity. Given orally 1, 5 or 24 hr before an i.v.
histamine challenge,
AHR-14310C produced ED50 values of 0.76, 0.22 and 0.58 mg/kg, respectively, in protecting naive guinea pigs from the lethal effects of the
histamine challenge.
AHR-14310C was also effective when the
histamine was administered as an
aerosol (1-, 5- and 24-hr ED50 values = 0.69, 0.38 and 1.08 mg/kg, respectively).
AHR-14310C also attenuated the anaphylactic responses to aerosolized
antigen in sensitive guinea pigs and the skin response to
antigen in naturally sensitive dogs.
AHR-14310C, at doses in vastly excess of those required to block
histamine-
induced hypotension, did not alter the electroencephalogram of cats, as did the sedating
antihistamine,
diphenhydramine.
AHR-14310C did not affect the autonomic responses to
acetylcholine,
isoproterenol,
epinephrine or 1,1-dimethyl-4-phenylpiperazinium
chloride in dogs. At low doses (0.316-1.0 mg/kg p.o.),
AHR-14310C blocked
antigen-induced tracheal mucous changes in sensitive rats.
AHR-14310C has therapeutic potential in allergic individuals, particularly in asthmatics, where bronchorrhea or mucus plugging is a problem.