Document Detail


Chemistry and synthetic development of misoprostol.
MedLine Citation:
PMID:  3932041     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Misoprostol is a synthetic prostaglandin which is related structurally to naturally occurring prostaglandin E1 (PGE1). PGE1 has long been recognized as an effective inhibitor of gastric acid secretion when administered intravenously. However, three major problems have prevented the use of natural PGE1 as a therapeutic treatment for peptic ulcer disease. Each of these problems, lack of oral activity, side-effects, and short duration of action, has been overcome by the chemical development of misoprostol from PGE1. The major structural alteration of PGE1 was the relocation of the 15-hydroxy group to the adjacent 16-position. This important modification significantly reduced typical prostaglandin side-effects such as diarrhea, yet retained full antisecretory potency and also provided a degree of oral activity. The second modification was the addition of a methyl group to carbon-16 to prevent metabolic oxidation of the hydroxy group. This structural change greatly increased both oral potency and duration of action and completed the synthetic development of misoprostol. Misoprostol is chemically unstable at room temperature, as is PGE1. This problem has been solved by pharmaceutical formulation studies which led to a stable and solid dosage form.
Authors:
P W Collins; R Pappo; E Z Dajani
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Digestive diseases and sciences     Volume:  30     ISSN:  0163-2116     ISO Abbreviation:  Dig. Dis. Sci.     Publication Date:  1985 Nov 
Date Detail:
Created Date:  1985-12-06     Completed Date:  1985-12-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7902782     Medline TA:  Dig Dis Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  114S-117S     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Alprostadil / adverse effects,  analogs & derivatives*,  chemical synthesis,  pharmacology
Animals
Anti-Ulcer Agents / chemical synthesis
Chemical Phenomena
Chemistry
Diarrhea / chemically induced
Drug Stability
Gastric Acid / secretion
Misoprostol
Prostaglandins E / classification
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Anti-Ulcer Agents; 0/Prostaglandins E; 59122-46-2/Misoprostol; 745-65-3/Alprostadil

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


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