Document Detail

Reviewing the mechanism of action of thiopurine drugs: towards a new paradigm in clinical practice.
MedLine Citation:
PMID:  15507865     Owner:  NLM     Status:  MEDLINE    
The precise mechanism of action of thiopurine drugs remains unclear despite more than 40 years of use. Recent knowledge in the field of apoptosis and a better insight into, as well as a rapid increase in their use in several important areas of clinical medicine justify this appraisal. This is a review of the recent advances in the knowledge of their mechanism of action and is primarily intended to help clinicians understand the pharmacological properties of these drugs adequately and to find ways to improve their use in clinical practice. The parent compound is azathioprine (AZA), which is rapidly reduced in the presence of glutathione to 6-mercaptopurine (6-MP) and then metabolized into active metabolites with immune-modifier activity. Recent observations and new data indicate that AZA/6-MP could be considered as a "two-in-one" drug, providing a source of 6-thioguanine nucleotides (6-TGNs) and methylated metabolites, and that both compounds could contribute to its antiproliferative effects. This review will also focus on mechanisms that may help to explain a number of recent observations showing that myelotoxicity may occur in patients with high TPMT level or low 6-TGN rate. Our final proposal suggests that the immunosuppressive effects of these drugs are due to a balanced combination of antimetabolic and pro-apoptotic actions.
Carlos J Cara; Amado Salvador Pena; Miquel Sans; Luis Rodrigo; Mercedes Guerrero-Esteo; Joaquín Hinojosa; Julio García-Paredes; Luis G Guijarro
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Publication Detail:
Type:  Journal Article; Review     Date:  2004-10-26
Journal Detail:
Title:  Medical science monitor : international medical journal of experimental and clinical research     Volume:  10     ISSN:  1234-1010     ISO Abbreviation:  Med. Sci. Monit.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-11-03     Completed Date:  2005-01-13     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  9609063     Medline TA:  Med Sci Monit     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  RA247-54     Citation Subset:  IM    
Scientific Department, Celltech Pharma, Madrid, Spain.
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MeSH Terms
Immunosuppressive Agents / metabolism,  pharmacology*
Purines / metabolism,  pharmacology*,  therapeutic use
Sulfur Compounds / metabolism,  pharmacology*,  therapeutic use
Reg. No./Substance:
0/Immunosuppressive Agents; 0/Purines; 0/Sulfur Compounds

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