Anti-inflammatory properties of tixocortol 17-butyrate,21-propionate (JO 1222), a novel, locally acting corticosteroid.
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.
Moodley
I
I
Institut de Recherche Jouveinal, Fresnes, France.
Grouhel
A
A
Lelièvre
V
V
Junien
J L
JL
D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D015777:Eicosanoids / Q000096:biosynthesis; D007249:Inflammation / Q000188:drug therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects; D011282:Pregnenediones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D015777:Eicosanoids; D011282:Pregnenediones; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; C069739:butixocort 21-propionate