Lodoxamide activity

Capron M, Loiseau S, Papin JR et al. Inhibitory effect of lodoxamide on eosinophU activation, hit Arch AUergy Immunol 1998 116 140-146. 

Aryloxamic acids, and aroylaminobenzoic acids Upjohn s aryloxamic acid, lodoxamide (U 42,585 E), (XCIV), is 2500 times more potent intravenously than DSCC f661. being the most potent agent thus far reported. However, this compound is 100-1000 fold less potent orally than intravenously, with inhibition in the PCA procedure obtained with oral doses between 0.1 and 10 mg/kg (g ) Activity has been reported in man following aerosol administration (fi7)- Further details on this series are discussed in the next chapter. 

Effect of Lodoxamide Guanylate Cyclases on Rat Lung Adenylate and (Basal Activity = 100%) ... 

We have reported studies on the effect of drugs on various lung parameters induced by Ascaris sensitivity (17.22). We quantitated these parameters and adapted the syston to test cromolyn Na by aerosol and intravenous administration as well as lodoxamide tromethamine. Lodoxamide tromethamine in this assay showed quantitative advantages to cromolyn Na (DSCX3) because it was significantly more active and was orally adsorbed. 

When lodoxamide tromethamine was administered orally to reactor Ascaris monkeys, excellent inhibition of both lung function parameters was seen Indicating a reversal of antigen challenge induced changes. Table 11 summarizes the activity of lodoxamide tromethamine and its duration of effect vAien dosed orally. This table also shows that when the optimal time (30 min.) is used to assay a dose response, inhibition can be seen as low as 5.0 mg/kg. Table 12 shows that when lodoxamide tromethamine was administered i.v. 5 min. before ascaris aerosolization (0.16 ml aerosolized in 50 respirations), protection was seen even at 0.001 mg total dose per animal (Table 13). 

Xanthine oxidase is a well known source of Oj. Rat pulmonary artery endothehal cells were found to have 53 8.57 units/10 cells of total xanthine oxidase -I- xanthine dehydrogenase activity, one unit defined as the conversion of 1 % of the substrate to product in 30 min of incubation (Phan et al. 1989). Xanthine oxidase comprised 31.6 3.1 % of this total activity. Addition of human neutrophils stimulated with 12-0-tetradecanoylphorbol-13-acetate caused a rapid and dose-dependent increase in rat pulmonary artery endothelial cell xanthine oxidase activity from 31.6 3.1% to 71.7 4.8% of total without altering total (xanthine oxidase + xanthine dehydrogenase) activity. Allopurinol, oxypurinol, and lodoxamide inhibited both enzyme conversion and cytotoxicity, catalase, superoxide dismutase, or deferoxamine failed to do so. 

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