Cromolyn structure

The chromone cromolyn sodium (5-5) was at one time considered the forerunner of a novel class of antiallergic and antiasthmatic drugs that act at one of the earliest stages of the allergic reaction. Detailed experiments, acmally conducted after the dmg s clinical effectiveness had been confirmed, suggested that the compound inhibited the release of mediators of the allergic reaction from mast cells. The dmg is not very active when taken orally and is usually applied topically to the lung by insufflation as its sodium salt. Considerable efforts to uncover additional structurally related mediator release inhibitors have had only limited success. 

Cromolyn sodium (disodium cromoglycate) and nedocromil sodium are stable but extremely insoluble salts (see structures below). When used as aerosols (by nebulizer or metered-dose inhaler), they effectively inhibit both antigen- and exercise-induced asthma, and chronic use (four times daily) slightly reduces the overall level of bronchial reactivity. However, these drugs have no effect on airway smooth muscle tone and are ineffective in reversing asthmatic bronchospasm they are only of value when taken prophylactically. 

Disodium cromoglycate (724), marketed as Intal or Cromolyn Sodium, bears some structural resemblance to khellin (457), the spasmolytic component of seeds of Ammi visnaga. Intal is one of the more successful drugs for the prevention of asthmatic attacks, though it is not effective in the treatment of an acute attack of asthma. It appears to prevent the release of histamine and other substances which mediate hypersensitivity reactions but is ineffective once these substances have been released. The chemistry and pharmacology of Intal have been reviewed (B-70MI22402). 

Structure IX Sodium cromoglicate (DSCG sodium cromo-glycate cromolyn sodium)... 

Synonyms Cromolyn sodium Disodium cromo-glycate Disodium salt of cromolyn Nasal-crom Intal Crolom Gastrocrom Chemical/Pharmaceutical/Other Class Mast cell stabilizing antiallergic agent Chemical Formula C23Hi4Na20n Chemical Structure ... 

Lodoxamide, which shows some structural similarities to cromolyn and nedocromil, also is a mast cell stabilizer that inhibits the immediate hypersensitivity reaction, preventing increases in vascular permeability associated with antigen-lgE-mediated responses. Its precise mechanism of action is not completely understood. It is used topically in the eye, principally for conjunctivitis and keratitis associated with vernal allergens. 

The calculated XRPD patterns show distinctly different peak positions and intensities for the reactant and product. This is because the loss of water results in an entirely new crystal structure, unlike the situation noted for cromolyn sodium [21], in which the lattice contracts upon water loss without changing the crystal form. XRPD patterns collected on samples stored at 31% and 70% relative humidity show similar behavior (Figs. 22a and 23a). Notice that several diffraction peaks not present in the calculated powder pattern of the reactant are present in the measured powder pattern of material stored at 70% RH (Fig. 22). The same situation is noted for the calculated XRPD... 

There are other compounds in the literature which seem to have a potentially useful blend of bronchodilator and antiallergy action. Compound IX, having a cromolyn-type structure, is effective in the passive cutaneous anaphylaxis test in rats as well as in the histamine aerosol test in guinea pigs (22). It has less cardiovascular effects than theophylline but causes some CNS stimulation. Compound X is a recent compound which in animals appears to be more potent than theophylline in its bronchodilator/antiallergic actions and also appears to have greater broncho-selectivity (23, 24). 

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