New corticoid 3-(2′-chloroethoxy)-6-formyl-9α-fluoro-δ 3,5-pregnadien derivatives in experimental allergy

Abstract

The anti-anaphylactic activity of some new synthetic corticoids in comparison to other known steroids was studied in several animal species. This class of compounds was shown to be particularly active in protecting mice against fatal anaphylactic shock. Among the water-insoluble steroids, the 3-(2′-chloroethoxy)-6-formyl-9α-fluoro-Δ 3,5-pregnadien - 11β, 16α, 17α, 21-tetrol-20-one-16α, 17α-acetonide-21-acetate (compound I) showed interesting activity both when given alone or combined with other drugs having different pharmacological actions. Especially at low doses (1 mg/kg i.m.) compound I was more active than prednisolone acetate, cortisone acetate, and cortisol acetate. A good synergistic action was demonstrated between this steroid, promethazine (anti-histamine) and MCE (anti-5HT). Compound I and cortisone acetate were also active in anaesthetized rats, in which they blocked the hypotension occurring when the challenge dose of serum was given to sensitized rats. The same two steroids were unable to protect guinea pigs from fatal anaphylaxis. Among the water-soluble steroids, 3-(2′-chloroethoxy)-6-formyl-9α-fluoro-Δ 3,5-pregnadien-11β, 16α, 17α, 21-tetrol-20-one-16α, 17α-acetonide-21-sodium hemisuccinate (compound II) was more active than dexamethasone sodium phosphate when given at a dose of 100 mg/kg i.p. only two hours before challenge, but was less active when the treatment-challenge interval was twenty hours, thus showing an immediate but short-lasting action.