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New Glucocorticoids on the Horizon: Repress, Don't Activate!
IN-HO SONG, RALF GOLD, RAINER H. STRAUB, GERD-RÜDIGER BURMESTER, and FRANK BUTTGEREIT ABSTRACT. Glucocorticoids are highly effective drugs; their immunosuppressive and antiinflammatory actions are used in the treatment of many rheumatic and other inflammatory diseases. However, their use is sometimes considerably limited by numerous adverse reactions. For this reason, great efforts have been made in recent years to develop innovative glucocorticoids or glucocorticoid receptor ligands that have improved therapeutic effect/adverse reaction ratio. We summarize the position and critically discuss the following products that are currently under development: (1) selective glucocorticoid receptor agonists (SEGRA or dissociating glucocorticoids); (2) nitrosteroids; and (3) long-circulating liposomal glucocorticoids. Finally, we describe the state of research on membrane-bound glucocorticoid receptors as possible further targets for specific glucocorticoid actions. (J Rheumatol 2005;32:1199-207) Key Indexing Terms: GLUCOCORTICOIDS From the Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin; Institute of Multiple Sclerosis Research, Department of Medicine, University of Goettingen, and the Hertie Foundation, Goettingen; and Department of Internal Medicine I, University Hospital, Regensburg, Germany. I-H. Song, MD; F. Buttgereit, MD, Professor; G-R. Burmester, MD, Professor, Department of Rheumatology and Clinical Immunology, Charité University Hospital; R. Gold, MD, Professor, Institute of Multiple Sclerosis Research, University of Goettingen; R.H. Straub, MD, Professor, Department of Internal Medicine I, University Hospital Regensburg. Address reprint requests to Prof. F. Buttgereit, Department of Rheumatology and Clinical Immunology, Charité University Hospital, Schumannstrasse 20/21, 10117 Berlin, Germany. E-mail: frank.buttgereit@charite.de Accepted for publication January 13, 2005. |