Inhibition of prostaglandin biosynthesis by tolfenamic acid in vitro.

@article{Lindn1976InhibitionOP,
  title={Inhibition of prostaglandin biosynthesis by tolfenamic acid in vitro.},
  author={I-B. Lind{\'e}n and Jouko Parantainen and Heikki Vapaatalo},
  journal={Scandinavian journal of rheumatology},
  year={1976},
  volume={5 3},
  pages={
          129-32
        }
}
The effect of tolfenamic acid on prostaglandin biosynthesis was investigated by using rabbit kidney medulla microsomal fraction, and the results compared with those obtained with indomethacin and acetylsalicylic acid. Tolfenamic acid inhibited the conversion of arachidonic acid to prostaglandin E2 very effectively and in a dose-dependent manner. IC50 values were 0.64 muM for tolfenamic acid, 0.76 muM for indomethacin, and 7 mM for acetylsalicylic acid. The inhibition of prostaglandin… 
Orally administered tolfenamic acid inhibits leukotriene synthesis in isolated human peripheral polymorphonuclear leukocytes
TLDR
It is suggested that inhibition of leukotriene synthesis is an additional mechanism of the anti-inflammatory, antimigraine and antidysmenorrhoeic effects of tolfenamic acid, and a possible explanation for its rare gastric and bronchoconstrictive side-effects.
MODULATION OF PROSTAGLANDIN BIOSYNTHESIS BY D-PENICILLAMINE AND GOLD DERIVATIVES
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Prostaglandin biosynthesis inhibitors and endometriosis.
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Effect of diclofenac sodium, tolfenamic acid and indomethacin on the production of superoxide induced by N-formyl-methionyl-leucyl-phenylalanine in normal human polymorphonuclear leukocytes.
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The effect of three non-steroidal anti-inflammatory drugs, diclofenac, indomethacin and tolfenamic acid, on the production of superoxide (O2-), by normal human polymorphonuclear leukocytes was studied, in vitro and it was concluded that the inhibition of O2- production is due to a combined effect on FMLP binding and on cellular O 2- metabolism.
Human metabolism of tolfenamic acid. II. Structure of metabolites and C-13 NMR assignments of fenamates
TLDR
Comparative studies on tolfenamic, mefenamic, and flufenamic acids in conjunction with the metabolites have permitted complete C-13 NMR assignments for this series of compounds.
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Abstract Tolfenamic acid is a potent prostaglandin synthetase inhibitor used clinically as non-steroidal anti-inflammatory and analgesic-antipyretic agent. A simple, sensitive, accurate, and precise
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TLDR
Tolfenamic acid proved to be a potent inhibitor of ex vivo thromboxane B2 generation in clotting blood and a potent inhibitors of prostaglandin E2 production in inflammatory exudate and significantly reduced the elevated skin temperature over carrageenan administered cages at all dose levels.
Pharmacodynamics and pharmacokinetics of tolfenamic acid in ruminating calves: evaluation in models of acute inflammation.
TLDR
The actions of tolfenamic acid in inhibiting PGE2 synthesis and in attenuating two of the cardinal signs of inflammation (heat and swelling) suggest that a dosage of 2 mgkg-1 administered intramuscularly should be effective clinically as an anti-inflammatory agent.
Non-Steroidal Anti-Inflammatory Analgesics Other than Salicylates
TLDR
Few clinically significant drug interactions are associated with concomitant administration of the arylalkanoic acids or piroxicam and other drugs, but there is a theoretical potential for displacement reactions with drugs that are used at plasma concentrations high enough to exceed the binding capacity of their own primary binding sites.
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References

SHOWING 1-10 OF 12 REFERENCES
INHIBITION OF THE PROSTAGLANDIN SYNTHETASE SYSTEMS IN OCULAR TISSUES BY INDOMETHACIN
TLDR
The differential sensitivity to inhibition of the prostaglandin synthetase systems from different tissues is an important consideration in the development of new ocular anti‐inflammatory agents.
The mode of action of aspirin and similar compounds.
  • J. Vane
  • Medicine
    The Journal of allergy and clinical immunology
  • 1976
TLDR
Evidence is reviewed which establishes this biochemical action as the basic mode of therapeutic action of aspirin-like drugs as anti-inflammatory, analgesic, and antipyretic compounds, which may also account for the shared side effects.
Effect of tolfenamic acid in rheumatoid arthritis.
TLDR
Tolfenamic acid appears to be a useful addition to the range of drugs suitable for the symptomatic treatment of rheumatoid arthritis.
Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs.
  • J. Vane
  • Chemistry, Medicine
    Nature: New biology
  • 1971
Experiments with guinea-pig lung suggest that some of the therapeutic effects of sodium salicylate and aspirin-like drugs are due to inhibition of the synthesis of prostaglandins.
A sensitive biological assay for prostaglandin E and acetylcholine
Superfused hamster stomach strip has been used in the bioassay of prostaglandin E2 (PGE2) and acetylcholine. The preparation proved very stable and had no spontaneous movements. The sensitivity to
The use of the hamster stomach in vitro as an assay preparation for prostaglandins
  • F. Ubatuba
  • Biology, Medicine
    British journal of pharmacology
  • 1973
TLDR
The results suggest that the hamster stomach preparation can be used to differentiate between 5‐hydroxytryptamine and prostaglandins.
Effects of anti-inflammatory drugs on prostaglandin biosynthesis.
TLDR
Comparison of the anti-inflammatory activities of several aspirin-like drugs with the inhibition of prostaglandin synthetase supports this as their mechanism of action.
Indomethacin and aspirin abolish prostaglandin release from the spleen.
The action of these two anti-inflammatory agents provides further support for the suggestion that some of their therapeutic effects depend on the inhibition of the production of prostaglandin.
New Aspects of the Mode of Action of Nonsteroid Anti-Inflammatory Drugs
This review surveys recent work on the possible mode of action and on the effects of that group of drugs variously known as non-narcotic analgesics, nonsteroidal anti-inflammatory drugs, aspirin-like
A double-blind clinical study on long-term use of oxyphenbutazone and tolfenamic acid in connection with telecobalt therapy.
TLDR
Tolfenamic acid appears to cause less side-effects than oxyphenbutazone in prolonged treatment, and this is in the light of the present and earlier studies.
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