Document Detail


Mechanisms of action of mycophenolate mofetil.
MedLine Citation:
PMID:  15803924     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mycophenolate mofetil (MMF, CellCept) is a prodrug of mycophenolic acid (MPA), an inhibitor of inosine-5'-monophosphate dehydrogenase. MPA depletes guanosine nucleotides preferentially in T and B lymphocytes and inhibits their proliferation, thereby suppressing cell-mediated immune responses and antibody formation. MPA also inhibits the glycosylation and expression of adhesion molecules, and the recruitment of lymphocytes and monocytes into sites of inflammation. MPA depletes tetrahydrobiopterin and decreases the production of nitric oxide by inducible NO synthase without affecting the activity of constitutive NO synthases. Activated macrophages produce NO and superoxide, which combine to generate tissue-damaging peroxynitrite. By these two mechanisms MMF exerts anti-inflammatory activity. Unlike calcineurin inhibitors, MMF is not nephrotoxic and does not induce the production of TGFbeta, which is fibrogenic. MMF does not increase blood pressure, cholesterol levels or triglyceride levels in recipients. MMF reduces acute and chronic rejection in allograft recipients and is efficacious in some nephropathies. Evidence is accumulating that MMF may have clinical utility in some autoimmune disorders.
Authors:
A C Allison
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Lupus     Volume:  14 Suppl 1     ISSN:  0961-2033     ISO Abbreviation:  Lupus     Publication Date:  2005  
Date Detail:
Created Date:  2005-04-04     Completed Date:  2005-07-28     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9204265     Medline TA:  Lupus     Country:  England    
Other Details:
Languages:  eng     Pagination:  s2-8     Citation Subset:  IM    
Affiliation:
SurroMed, Inc, Menlo Park, CA 94025, USA. aallison@surromed.com
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MeSH Terms
Descriptor/Qualifier:
Azathioprine / pharmacology
B-Lymphocytes / drug effects
Cytokines / biosynthesis,  drug effects
Humans
Immunosuppressive Agents / pharmacology*,  therapeutic use
Mycophenolic Acid / analogs & derivatives*,  pharmacology*,  therapeutic use
Nitric Oxide / biosynthesis
T-Lymphocytes / drug effects
Vascular Diseases / prevention & control
Chemical
Reg. No./Substance:
0/Cytokines; 0/Immunosuppressive Agents; 10102-43-9/Nitric Oxide; 24280-93-1/Mycophenolic Acid; 446-86-6/Azathioprine; 9242ECW6R0/mycophenolate mofetil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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