Tixocortol 17-butyrate,21-propionate (
JO 1222) is a novel, locally acting,
C-21 thioester-linked
corticosteroid with significant activity in a number of models of
inflammation. In models of acute
inflammation,
JO 1222 had an ED30 of 3 micrograms in
carrageenan-induced oedema, an ED50 of 5 ng in
croton oil-induced
inflammation, and 4 micrograms and 2 micrograms/pleural cavity in
carrageenin-induced
pleurisy in the rat and mouse respectively. In a model of subchronic
inflammation JO 1222 had an ED50 of 39 micrograms/pellet (cotton pellet-induced
granuloma) and an ED50 of 13 ng in
oxazolone-induced
hypersensitivity. The overall relative potency was found to be
beclomethasone DP greater than
betamethasone DP =
JO 1222 greater than
hydrocortisone 17-butyrate,21-propionate greater than
hydrocortisone acetate. In contrast to any of the other
corticosteroids, including
beclomethasone DP,
JO 1222 did not have any marked systemic effects in any of the above models following oral or local administration. Furthermore, in contrast to other locally acting
corticosteroids such as
beclomethasone DP,
JO 1222 had little or no effect on the thymus or
body weight. These findings suggest that
JO 1222 is a novel, potent, locally acting
corticosteroid with little or no systemic effects and thus has therapeutical potential in diseases such as
asthma,
arthritis,
ulcerative colitis and
rhinitis.