Local Anti-inflammatory Activity and Systemic Side Effects of NM-135, a New Prodrug Glucocorticoid, in an Experimental Inflammatory Rat Model

• Published in: Japanese Journal of Pharmacology Vol. 78; no. 4; pp. 505 - 509
• Main Authors: Takayuki, Ishii, Nobuyuki, Kibushi, Takashi, Nakajima, Tae, Kakuta, Noriko, Tanaka, Chiaki, Sato, Kei, Sugai, Isao, Kijima-Suda, Hirofumi, Kai, Takeshi, Miyata
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Pharmacological Society 1998
• Subjects: Animals; Anti-Inflammatory Agents - adverse effects; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Atrophy - chemically induced; Betamethasone Valerate - pharmacology; Betamethasone Valerate - therapeutic use; Croton Oil - administration & dosage; Croton Oil - adverse effects; Diflucortolone - analogs & derivatives; Diflucortolone - pharmacology; Diflucortolone - therapeutic use; Disease Models, Animal; Dose-Response Relationship, Drug; Ear - pathology; Edema - chemically induced; Edema - drug therapy; Edema - pathology; Exudates and Transudates - drug effects; Glucocorticoid; Glucocorticoids - adverse effects; Glucocorticoids - pharmacology; Glucocorticoids - therapeutic use; Granuloma - chemically induced; Granuloma - drug therapy; Inflammation - chemically induced; Inflammation - drug therapy; Male; Organ Size - drug effects; Pregnanediones; Prodrug; Prodrugs - adverse effects; Prodrugs - pharmacology; Prodrugs - therapeutic use; Rats; Rats, Sprague-Dawley; Systemic side effect; Thymus Gland - drug effects; Thymus Gland - pathology; Glucocorticoid; Systemic side effect; Prodrug
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.78.505

The local anti-inflammatory activity and systemic side effects of NM-135 (6α,9-difluoro-11β-hydroxy-16α-methyl-21[[2,3,4,6-tetrakis-O-(4-methylbenzoyl)-β-D-glucopyranosyl]oxy]-pregna-1,4-diene-3,20-dione) in croton oil-induced granuloma pouches and ear edema in rats were studied. The local antiinflammatory activity of NM-135 was stronger than that of betamethasone 17-valerate (BV). As to systemic side effects, BV and diflucortolon valerate (DFV) caused thymolysis at the doses required for the antiinflammatory activity. In contrast, no clear systemic side effect was observed in rats administered NM-135 at the dose producing the anti-inflammatory activity. These results suggest that NM-135 is a drug exhibiting a high degree of dissociation between the local anti-inflammatory activity and systemic side effects.