Darmstoff analogues. 3. Actions of choline esters of acetal phosphatidic acids on visceral smooth muscle

J Med Chem. 1989 Jun;32(6):1319-22. doi: 10.1021/jm00126a029.


A number of naturally occurring phospholipids, e.g. the acetal phosphatidic acid derivatives that comprise Darmstoff (1) and the phosphatidylcholine derivative platelet activating factor (PAF), cause contraction of certain visceral smooth muscles and cause platelet activation. Because the Darmstoff phosphatidic acids and PAF are structurally similar, it was of interest to compare the biological actions of choline esters of Darmstoff with those of PAF and of the parent Darmstoff phosphatidic acids. To this end, [(2-pentadecyl-1,3-dioxolan-4-yl)methyl]phosphocholine (3a), [[2-(cis-8-heptadecenyl)-1,3-dioxolan-4-yl]methyl]phosphocho line (3b), and [[2-(cis-8-pentadecenyl)-1,3-dioxolan-4-yl]methyl]phosphocho line (3c) were synthesized. Compounds 3a, 3b, 3c, and PAF caused dose-dependent relaxation of taenia coli strips. In contrast, the unesterified materials 1a and 1b, as well as lyso-PAF, caused contraction in taenia coli strips. Thus, the contractile effect of Darmstoff is reversed on esterification with choline. In preparations of whole trachea, both 1a and 3a had contractile effects similar to those of PAF.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chemical Phenomena
  • Chemistry
  • Choline / chemical synthesis
  • Choline / pharmacology*
  • Colon / drug effects
  • Colon / physiology
  • Dose-Response Relationship, Drug
  • Esterification
  • Esters / chemical synthesis
  • Esters / pharmacology
  • Guinea Pigs
  • Molecular Structure
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology*
  • Phosphatidic Acids / chemical synthesis
  • Phosphatidic Acids / pharmacology*
  • Platelet Activating Factor / pharmacology
  • Structure-Activity Relationship
  • Trachea / drug effects
  • Trachea / physiology


  • Esters
  • Phosphatidic Acids
  • Platelet Activating Factor
  • Choline