The long duration, in vivo, inhibition of prostaglandin synthetase by 2-methyl-8-cis-12-trans-14-cis-eicosatrienoic acid.
Competitive inhibition of prostaglandin synthetase by 8-cis-12-trans-14-cis-eicosatrienoic acid has been reported to occur in vitro. No in vivo effects were observed, possibly due to rapid metabolic degradation of this fatty acid by beta-oxidation. The present study involved the evaluation of this compound in vivo, and the preparation and evaluation in vivo of its alpha and beta methyl-substituted analogs which retain the carbon skeleton of the parent compound, and which might be expected to be resistant to beta-oxidation. Using a newly developed radioimmunoassay for the total urinary metabolites of prostaglandin E, data were obtained that indicates that both the parent compound and its 2-methyl analog are prostaglandin synthetase inhibitors in vivo. The 2-methyl analog exhibited an unusually long duration of activity as compared to both indomethacin and the parent compound. The lengthened duration of action of the 2-methyl analog may be explained both by its possible resistance to beta-oxidation, and to possible alteration in rates of either fatty acid transport, or incorporation/release from triglycerides (acylation/deacylation of triglycerides).
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; C045515:2-methyl-8,12,14-eicosatrienoic acid; D015126:8,11,14-Eicosatrienoic Acid; D007213:Indomethacin