The development of Wy-41,195, an orally effective antiallergic drug in animal models

doi:10.1007/BF01964989

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The development of Wy-41,195, an orally effective antiallergic drug in animal models

Published Jun 1, 1986 · A. Lewis, R. Carlson, T. Forster

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Abstract

Introduction Disodium cromoglycate (DSCG) administered by aerosol is well established as a prophylactic treatment for asthma. Since it is not effective orally and does not benefit all asthmatics, the search for a more potent and orally effective analog has attracted the attention of numerous pharmaceutical companies [1, 2]. Unfortunately, a poor correlation exists between preclinical screening models and clinical activity [3]. The former are based on the premise that DSCG stabilizes mast cell membranes and prevents the release of allergic mediators induced by antigen-cell bound IgE interaction. This review is an account of the preclinical and clinical development of Wy-41,195 (Fig. 1), an orally effective antiallergic compound. It was originally selected from a series of oxanilic acids [4] that were effective in rat passive cutaneous anaphylaxis (PCA), a screening test adopted for predicting DSCG-like antiallergic activity. However, in addition to its action on the mast cell, DSCG inhibits reflex bronchoconstriction in dogs [5] and bronchoconstriction induced in man by hyperventilation [6], cold air [7] and SO2 [8], events not associated with mast cell activation. Consequently, we have also examined the effects of Wy-41,195 in preclinical models involving reflex bronchoconstriction and airways hyperresponsiveness.

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Key takeawayWy-41,195 is an orally effective antiallergic compound that shows potential in treating asthma and other allergic conditions by stabilizing mast cell membranes and inhibiting reflex bronchoconstriction.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

The development of Wy-41,195, an orally effective antiallergic drug in animal models

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References

Inhibition of sulfur dioxide-induced bronchoconstriction by disodium cromoglycate in asthmatic subjects.

Cromolyn inhibits sulfur dioxide-induced bronchoconstriction in asthmatic subjects, potentially through a mechanism independent of its effect on mast cells.

The effects of antiallergic and bronchodilator drugs on platelet-activating factor (PAF-acether) induced bronchospasm and platelet aggregation

Thiazinamium chloride effectively inhibits bronchospasm and platelet aggregation induced by platelet-activating factor, potentially benefiting asthma patients.

Alteration of drug responsiveness in guinea-pig lung anaphylaxis using different antigen challenge concentrations

Antihistamine-resistant bronchospasm in guinea pigs increases with higher antigen concentrations, potentially due to SRS-A release.

Mechanisms of sulphur dioxide induced bronchoconstriction in normal and asthmatic man.

Atropine and sodium cromoglycate inhibit sulphur dioxide-induced bronchial response in normal subjects, but vagal mechanisms are not important in hyperreactivity to SO2.

BACKGROUND AND PRESENT STATUS OF RESEARCH ON PLATELET‐ACTIVATING FACTOR (PAF‐ACETHER)

PAF-acether is a phospholipid mediator that activates platelets and is a key player in platelet-mediated blood clotting.

THE ACTIVITY OF SODIUM CROMOGLYCATE ANALOGUES IN HUMAN LUNG in vitro: A COMPARISON WITH RAT PASSIVE CUTANEOUS ANAPHYLAXIS AND CLINICAL EFFICACY

Sodium cromoglycate analogues show more potent histamine suppression in human lung than in rat passive cutaneous anaphylaxis, but their clinical effectiveness is less effective than sodium cromoglycate.

THE EFFECTS OF SODIUM CROMOGLYCATE ON LUNG IRRITANT RECEPTORS AND LEFT VENTRICULAR CARDIAC RECEPTORS IN THE ANAESTHETIZED DOG

Sodium cromoglycate in dogs produces reflex hypotension and reverses histamine-induced reflex bronchoconstriction by activating receptors in the left ventricle of the heart.

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