The use of corticosteroids in the treatment of inflammatory conditions has been limited primarily due to their systemic suppressive effects on the adrenal function and the immune system. To overcome this limitation, a focused effort has been made to synthesize locally active antiinflammatory steroids without systemic adverse effects based on the antedrug concept. In this approach, metabolically labile functional groups, alkyl carboxylates at various strategic positions of potent corticosteroids, have been introduced. The reduced systemic adverse effects of this steroidal antedrug are ascribed to rapid hydrolysis of the ester function into an inactive steroid acid upon entry into the circulation system. Thus the true antedrug acts only locally. It is proposed to synthesize a new group of steroidal antedrugs and evaluate them comprehensively with respect to their local and systemic pharmacological activity. To further delineate the mode of action of the new steroids, their receptor binding characteristics, effects on pituitary adrenal function, glycogen deposition, liberation of prostanoids and elastase will b studied. Results of these studies will yield valuable insight into the structural characteristics for the maximum separation of local anti-inflammatory activity from systemic adverse effects, and mode of action of these new steroids with the promise of providing a solid rational basis for development of new potent anti-inflammatory steroids devoid of systemic side effects.

Project Start
1998-05-01
Project End
1999-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
26
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Florida Agricultural and Mechanical University
Department
Type
DUNS #
City
Tallahassee
State
FL
Country
United States
Zip Code
32307
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