Antiallergic properties of SQ 13,847, an orally effective agent. I. Activity in vivo.

A structurally novel pyrazolo[1,5-c]quinazoline, SQ 13,847, was demonstrated to be an orally active antiallergic agent. The compound inhibited immunoglobulin (Ig)E-mediated passive cutaneous anaphylaxis (PCA) and passive pulmonary anaphylaxis in the rat (ID50 = 2 to 4 mg/kg p.o.), but failed to affect IgG-mediated PCA in the rat, IgE-mediated PCA in the mouse or IgG1-mediated PCA in the guinea pig. The relative potencies of SQ 13,847 and its 2-carboxylic acid metabolite, SQ 12,903, upon oral vs. intravenous administration were consistent with a role of SQ 13,847 as an orally absorbed prodrug of SQ 12,903. In the rat, SQ 13,847 is not an antagonist of histamine in serotonin, in beta adrenergic agonist or a bronchodilator.

Effect of Ascaris suum and other adjuvants on the potentiation of the IgE response in guinea-pigs.

The potentiation effect of various adjuvants on the production of guinea-pig IgE was investigated using Freund's complete and incomplete adjuvant, the lipopolysaccharide of Escherichia coli and Salmonella typhosa, Bordetella pertussis, and the nematodes Nippostrongylus brasiliensis and Ascaris suum. While all the antigens had a variable effect on the potential of the IgG response, only infection with A. suum resulted in an enhanced IgE response to the antigen, egg albumin. Maximum potentiation occurred when primary immunization and nematode infection were accomplished simultaneously.

Dependence of the guinea pig IgE and IgG1 immune responses on the inclusion of potassium in the preparation of alum adjuvant.

Primary immunization with alum prepared using AlK(SO4)2 and adjuvant enhanced IgE production in the guinea pig. Alum prepared from Al2 (SO4)3 showed greatly reduced IgE and IgG1 anti-EA titers. This variance in immunoglobulin titer was observed only in the guinea pig. Both rats and mice respond to alum preparations prepared from either AlK(SO4)2 or Al2(SO4)3 equally as well.