A new inhibitor of IgE-mediated allergic reactions has been studied in rats. This new inhibitor is chemically different from cromoglycate and shows qualitative and quantitative advantages over it. It is 2,500 times more active in rats than disodium cromoglycate and shows oral activity. This new inhibitor possesses no bronchodilator or end-organ antagonism activity and does not raise intracellular cAMP levels but as cromoglycate acts by inhibition of mediator release. Multiple high (25 mg/kg) doses in rats lead to tachyphylaxis. This effect is reversed both by decreasing the first dose and increasing the time between doses. Over a 5- to 10-fold concentration range, this inhibitor in mast cells can be stimulatory or inhibitory to ⁴⁵Ca⁺⁺ flux into cells. This ability to inhibit ionophore-induced ⁴⁵Ca⁺⁺ flux correlates well with inhibition of histamine release.

Airway obstruction and hyperreactivity are characteristics of human asthma and of "heaves," a naturally occurring respiratory disorder of horses and ponies. To document the role of cyclooxygenase products of arachidonic acid metabolism in the pathogenesis of heaves, we measured plasma and bronchoalveolar lavage (BAL) fluid concentrations of metabolites of thromboxane (TX)A2 and prostaglandins (PG) I2 and D2 in five affected ponies and their age- and gender-matched controls prior to and during acute airway obstruction precipitated by housing the ponies in a barn and exposing them to hay dust. Pulmonary resistance increased significantly and dynamic compliance and arterial oxygen tension decreased significantly in affected ponies that were placed in the barn. At this time, histamine aerosol challenge demonstrated the presence of airway hyperresponsiveness in the affected ponies. Plasma TXB2 was the only metabolite that increased significantly during the acute disease state. In a subsequent experiment, the ponies were treated with flunixin meglumine, a cyclooxygenase inhibitor, to determine if this would alter the onset or development of clinical disease. At a dose of 1.1 mg/kg intramuscularly, 3 times daily, flunixin meglumine inhibited TXB2 production but did not alter the degree of airway obstruction or airway hyperreactivity measured at pasture and in the barn. We conclude that cyclooxygenase products of arachidonic acid metabolism are altered but do not play a role in the airway obstruction and hyperreactivity observed in ponies with heaves.

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Immediate type hypersensitivity to Ascaris antigen in rhesus reactor monkeys was used to assess the pharmacologic profile of Cromolyn Na and a new inhibitor of IgE-medited lung function changes. Cutaneous reactivity to Ascaris correlated poorly with a respiratory response to the antigen. Two parameters used to measure lung function, respiratory rate increase and tidal volume decrease, were significantly altered by Cromolyn Na and compound A.