AHR-14310C: a potent, long-acting, nonsedating H1-antihistamine that prevents antigen-induced mucus formation in sensitive rats.

Abstract

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.

• Authors: J C Nolan, M H Foxwell, L L Whitman, J M Yanni, D A Walsh, B F Kilpatrick, D N Johnson, A G Proakis
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 253 Issue 3 Pg. 1177-83 (Jun 1990) ISSN: 0022-3565 [Print] United States
• PMID: 1972750 (Publication Type: Journal Article)

Chemical References

• Histamine Antagonists
• Histamine H1 Antagonists
• Oxazoles
• Oxazolidinones
• Piperidines
• AHR 14310C
• Acetylcholine

Topics

• Acetylcholine (antagonists & inhibitors)
• Animals
• Cats
• Dogs
• Drug Hypersensitivity (drug therapy)
• Female
• Guinea Pigs
• Histamine Antagonists (pharmacology)
• Histamine H1 Antagonists (metabolism, pharmacology)
• Male
• Muscle, Smooth (drug effects)
• Oxazoles (metabolism, pharmacology)
• Oxazolidinones
• Piperidines (metabolism, pharmacology)
• Rats
• Rats, Inbred Strains
• Skin Tests
• Sleep (drug effects)