In vivo anti-allergic and bronchopulmonary pharmacology of REV 3164 in rats and guinea-pigs.

Abstract

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.

• Authors: M Leibowitz, R J Gordon, P S Wolf, P Sonnino-Goldman
• Journal: Archives internationales de pharmacodynamie et de therapie (Arch Int Pharmacodyn Ther) Vol. 271 Issue 1 Pg. 135-54 (Sep 1984) ISSN: 0003-9780 [Print] Belgium
• PMID: 6497506 (Publication Type: Journal Article)

Chemical References

• Histamine Antagonists
• Immunoglobulin G
• Parasympatholytics
• Quinoxalines
• SRS-A
• Serotonin Antagonists
• Triazoles
• Immunoglobulin E
• p-Methoxy-N-methylphenethylamine
• 7-chloro-5-propyl-1,2,4-triazolo(4,3-a)quinoxaline-1,4(2H,5H)-dione

Topics

• Animals
• Antibody Formation (drug effects)
• Asthma (physiopathology)
• Bronchi (drug effects)
• Guinea Pigs
• Histamine Antagonists (pharmacology)
• Immunoglobulin E (immunology)
• Immunoglobulin G (immunology)
• Male
• Parasympatholytics (pharmacology)
• Passive Cutaneous Anaphylaxis (drug effects)
• Quinoxalines (pharmacology)
• Rats
• Rats, Inbred Strains
• Respiratory System (drug effects)
• SRS-A (physiology)
• Serotonin Antagonists (pharmacology)
• Species Specificity
• Time Factors
• Triazoles
• p-Methoxy-N-methylphenethylamine (antagonists & inhibitors)