TY - JOUR T1 - The Specific Type-4 Phosphodiesterase Inhibitor Mesopram Alleviates Experimental Colitis in Mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 549 LP - 556 DO - 10.1124/jpet.102.039529 VL - 305 IS - 2 AU - Florian Loher AU - Kathrin Schmall AU - Philipp Freytag AU - Nikola Landauer AU - Roland Hallwachs AU - Christian Bauer AU - Britta Siegmund AU - Florian Rieder AU - Hans-Anton Lehr AU - Marc Dauer AU - Joachim Friedrich Kapp AU - Stefan Endres AU - Andreas Eigler Y1 - 2003/05/01 UR - http://jpet.aspetjournals.org/content/305/2/549.abstract N2 - Mesopram, a specific inhibitor of type-4 phosphodiesterase, decreases the synthesis of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In the present study, we investigated the effect of mesopram in dextran sulfate sodium (DSS)-induced murine colitis. In the preventive model, colitis was induced by DSS simultaneously with the application of mesopram in BALB/c mice. In the therapeutic model, colitis was induced in BALB/c mice by DSS over 7 days. At day 8, DSS was discontinued, and treatment was started. Mesopram was applied intraperitoneally or orally. The clinical score was calculated daily during the course of each study. Post mortem, colon length, histologic score, and expression of TNF-α and IFN-γ in colons were determined. In the preventive model, mesopram significantly reduced the maximal clinical score, decreased colon shortening, and the histologic score. A dose finding study, using the preventive model, showed that most clinical and post mortem benefit was achieved with 50 mg/kg mesopram compared with 2 and 10 mg/kg. In the therapeutic model, i.p. mesopram treatment led to a significant reduction of clinical score. Both, i.p. and p.o. mesopram significantly reversed DSS-induced colon shortening and reduced the ex vivo colonic production of IFN-γ. We conclude that the specific type-4 phosphodiesterase inhibitor mesopram ameliorates murine colitis both in a preventive and a therapeutic setting. The American Society for Pharmacology and Experimental Therapeutics ER -