In vivo anti-allergic and bronchopulmonary pharmacology of REV 3164 in rats and guinea-pigs.
REV 3164 has been evaluated in a variety of intact rodent models to reveal potential utility in the prophylactic treatment of asthma. REV 3164 was found a potent, orally active inhibitor of rat (IgE) passive cutaneous anaphylaxis (PCA, ED50 = 0.9 mg/kg). By contrast, at 50-200 mg/kg p.o., it did not affect guinea-pig (IgG1) PCA. In PCA rats, both REV 3164, 1-36 mg/kg i.p., and the known inhibitor of mast cell mediator release, disodium cromoglycate (DSCG), 2-54 mg/kg i.p., blocked cutaneous wheals caused by i.v. antigen challenge but not by intradermal serotonin or histamine. Neither REV 3164 (0.1-10 mg/kg i.p.) nor DSCG (2-54 mg/kg i.p.) affected Compound 48/80-induced wheals. REV 3164 (0.01-1 mg/kg i.v. or 10 mg/kg i.p.) abolished rat (IgE) passive lung anaphylaxis (PLA, ED50 = 0.05 mg/kg i.v. for inhibition of elevated airway resistance). At 10 mg/kg i.p., REV 3164 did not affect active lung anaphylaxis in guinea-pigs pharmacologically manipulated to enhance the production and action of slow reacting substance of anaphylaxis (SRS-A), nor did it exhibit anticholinergic activity in the rat. REV 3164 (100 mg/kg i.p.) did not protect conscious guinea-pigs from histamine aerosol-induced collapse. It is concluded that REV 3164 is an oral inhibitor of IgE-dependent immediate hypersensitivity in the rat with biological activities in rats and guinea-pigs similar to DSCG.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012137:Respiratory System / Q000187:drug effects*; D013189:SRS-A / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013045:Species Specificity; D013997:Time Factors; D014230:Triazoles; D003189:p-Methoxy-N-methylphenethylamine / Q000037:antagonists & inhibitors
D006633:Histamine Antagonists; D007074:Immunoglobulin G; D010276:Parasympatholytics; D011810:Quinoxalines; D013189:SRS-A; D012702:Serotonin Antagonists; D014230:Triazoles; D007073:Immunoglobulin E; D003189:p-Methoxy-N-methylphenethylamine; C040270:7-chloro-5-propyl-1,2,4-triazolo(4,3-a)quinoxaline-1,4(2H,5H)-dione