Cromoglycate

Chloro-oxazolo[4,5-/i]quinoline-2-carboxylic acid methyl ester was the most active compound in tests for inhibitors of antigen-induced release of histamine in vitro from rat peritoneal mast cells (IC50 of 0.3 p,M) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (ED50 (intraperitoneal) of 0.1 mg/kg in dose 0.5 mg/kg as an inhibitor of the test)—10 times and 60 times more potent, respectively, than the disodium salt of cromoglycic acid (85JMC1255). 

Alkylation of the dihydroxyacetophenone, 44, with epichloro-hydrin results in condensation of two molecules of the phenol with the latent glycerol (45). Reaction of the intermediate with ethyl oxalate affords the chromone ester, 46. Saponification leads to the bronchiodilator cromoglycic acid (47). The agent is usually administered by oral insufflation as its extremely insoluble disodium salt. 

Carboxylic acid derivatives of heterocycles have proved a source of compounds that show the same allergic mediator release inhibiting activity as sodium cromoglycate. A number of these agents have been taken to the clinic for trial as antiallergic agents. 

Both disodium cromoglycate and nedocromil sodium have antitussive effects in humans. In this instance, their activity occurs by increasing the depolarisation of sensory nerves, which increases the threshold for an action potential and therefore inhibits the activity of these neurons. 

Kellaway, I. W., Taylor, K. G. M., Taylor, G., and Stevens, J. (1988). The pharmacokinetics of liposomal sodium cromoglycate nebulized to volunteers, Proc. Int. Symp. Control. Rel. Bioact. Mater.. 15, 197-198. 

Snake venoms, neuroactive, 21 (1984) 63 Sodium cromoglycate analogues, 21 (1984) 1... 

JH Bell, NA Stevenson, JE Taylor. A moisture transfer effect in hard gelatin capsules of sodium cromoglycate. J Pharm Pharmacol 25 (suppl) 96P-103P, 1973. 

MT Vidgren, PA Vidgren, TP Paronen. Comparison of physical and inhalation properties of spray-dried and mechanically micronized disodium cromoglycate. Int J Pharm 35 139-144, 1987. 

Fig. 10 Release of cromolyn sodium (sodium cromoglycate) from human serum albumin microspheres prepared using a water-oil emulsion technique with 5% glutaraldehyde as cross-linking agent. Dissolution medium pH 7 phosphate buffer. (From Ref. 98.)... 

Wilson, C. G. Tomlinson, E. Davis, S. S. Olejnik, O., Altered ocular absorption and disposition of sodium cromoglycate upon ion-pair and complex coacervate formation with dodecylbenzyldimethyl-ammonium chloride, J. Pharm. Pharmacol. 31, 749-753 (1981). 

Figure 4.5. Plasma histamine levels in response to NT in rats pretreated with saline or disodium cromoglycate (100 pg). NT (5 nmol/kg) or saline (0.3 ml) was given intravenously. Mean + S.E.M. of n experiments, quoted with the column.

Curry, S.H., Taylor, A.X, Evans, S., Godfrey, S. and Zeidifard, E. (1975). Disposition of disodium cromoglycate administered in three particle sizes. Br. J. Clin. Pharmacol. 2 267-270. 

Godfrey, S., Zeidifard, E., Brown, K. and Bell, J.H. (1974). The possible site of action of sodium cromoglycate assessed by exercise challenge. Clin. Sci. Mol. Med. 46 265-272. 

Oxalate is found to be a frequent impurity in pharmaceutical substances belonging to the category of either organic acids e.g.. anhydrous citric acid, tartaric acid or salts of organic acids e.g., ferrous gluconate, sodium citrate, potassium citrate and sodium cromoglycate. The presence of this impurity is due to the following two prime factors, namely ... 

T. Mori, K. Nishimura, S. Tamaki, S. Nakamura, H. Tsuda, N. Kakeya, Prodrugs for the Oral Delivery of Disodium Cromoglycate , Chem. Pharm. Bull. 1988, 36, 338-344. 

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