Inhibitory effect of HSR-6071, a new anti-allergic agent, on experimental asthma in rats and guinea-pigs.

Abstract

The experimental asthma caused by IgE antibody in rats was inhibited by HSR-6071 (6-(1-pyrrolidinyl)-N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamide) (0.01-0.1 mg kg-1 i.v.) in a dose-dependent manner. The inhibitory activity of HSR-6071 was more potent than those of disodium cromoglycate and ketotifen, and equipotent with amlexanox. The bronchoconstriction mediated by IgE or IgG antibody in guinea-pigs was also prevented by HSR-6071 (0.3, 1 and 3 mg kg-1 i.v.), amlexanox (3, 10 and 30 mg kg-1 i.v.) and ketotifen (0.1 mg kg-1 i.v.) but not by disodium cromoglycate (10 mg kg-1 i.v.). HSR-6071 was more potent than amlexanox, but less potent than ketotifen. HSR-6071 suppressed antigen-induced histamine and SRS-A release from minced lung tissues of guinea-pigs sensitized passively with rabbit anti-EA serum and was a more potent inhibitor of the release of SRS-A than of histamine. On the other hand, histamine- or acetylcholine-induced bronchoconstriction in guinea-pigs was scarcely affected by HSR-6071 at doses sufficient to inhibit the experimental asthma, but LTD4-induced bronchoconstriction was dramatically inhibited. These results indicate that the inhibitory action on experimental allergic asthma of HSR-6071 may be due to suppression of antigen-induced histamine and SRS-A release from lung tissues and to antagonism of SRS-A action. In addition, HSR-6071 inhibited cyclic AMP phosphodiesterase activity and produced relaxation of the guinea-pig isolated trachea. These pharmacological actions may contribute to the production of the anti-allergic action of HSR-6071.

• Authors: E Makino, T Ohashi, H Takahashi, H Kato, Y Ito, H Nagai, A Koda, H Azuma
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 42 Issue 4 Pg. 236-41 (Apr 1990) ISSN: 0022-3573 [Print] England
• PMID: 1974289 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Aminopyridines
• Azoles
• Pyrrolidines
• SRS-A
• Tetrazoles
• HSR 6071
• Immunoglobulin E
• Histamine
• amlexanox
• 3',5'-Cyclic-AMP Phosphodiesterases
• Cromolyn Sodium
• Ketotifen

Topics

• 3',5'-Cyclic-AMP Phosphodiesterases (antagonists & inhibitors)
• Aminopyridines (therapeutic use)
• Animals
• Asthma (drug therapy)
• Azoles (therapeutic use)
• Bronchi (drug effects)
• Cromolyn Sodium (therapeutic use)
• Female
• Guinea Pigs
• Histamine (pharmacology)
• Hypersensitivity (drug therapy)
• Immunoglobulin E (immunology)
• In Vitro Techniques
• Ketotifen (therapeutic use)
• Lung (drug effects, metabolism)
• Male
• Muscle Relaxation (drug effects)
• Muscle, Smooth (drug effects)
• Passive Cutaneous Anaphylaxis (drug effects)
• Pyrrolidines (therapeutic use)
• Rabbits
• Rats
• Rats, Inbred Strains
• SRS-A (blood, metabolism)
• Tetrazoles (therapeutic use)