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Colchicine Analogues in Experimental Murine Amyloidogenesis

  • Mordechai Ravid
  • Maya Gotfried
  • Jack Bernheim
  • Baruch Chen
  • Arnold Brossi
Chapter

Abstract

Colchicine is a widely used preparation in diverse clinical settings such as gout, familial Mediterranean fever, AA amyloidosis, liver fibrosis and Bechet’s disease. It also has an antimitotic potential hitherto unexplored due to its narrow therapeutic toxic ratio.

Data is presented on the effectiveness and toxicity of three colchicine analogues: thiocolchicine, 2, 3 didemethylcolchicine and 3-demethyl-thiocolchicine in the blockage of amyloid synthesis in a murine model.

3-Demethylthiocolchicine was found as effective as colchicine in blocking anyloidogenesis. Doses three times higher than those of colchicine were well tolerated. The other two compounds were either less effective or toxic.

3-Demethylthiocolchicine shows tubulin binding, anti inflammatory activity and antimitotic effect similar to those of colchicine while doses 3 to 10 times higher than colchicine were well tolerated by different experimental animals. This preparation therefore carries the potential to replace colchicine as standard therapy for FMF and possibly also for other diseases now treated by colchicine.

Keywords

Liver Fibrosis Primary Biliary Cirrhosis Familial Mediterranean Fever Acute Gouty Arthritis Saline Treated Control Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Mordechai Ravid
    • 1
    • 2
  • Maya Gotfried
    • 1
    • 2
  • Jack Bernheim
    • 1
    • 2
  • Baruch Chen
    • 1
    • 2
  • Arnold Brossi
    • 1
    • 2
  1. 1.Department of Medicine and Pathology, Sackler School of MedicineTel Aviv UniversityIsrael
  2. 2.Laboratory of Medicinal Chemistry NIDDKNational Institutes of HealthBethesdaUSA

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