Indomethacin binding

Further experiments later showed that the more potent PG synthetase inhibitor, indomethacin, can inhibit aspirin acetylation at 1 flM levels. However, indomethacin binding is reversible by treatment with aspirin at several 1 hour intervals, which resulted in complete acetylation of the enzyme. 

Young That s a good point. I have seen that indomethacin not only does prostaglandin inhibition but there also are other mechanisms, possibly as simple as intracellular binding of Ca2+ in terms of buffer. However, what you are saying is entirely possible. 

The actions of non-steroidal anti-inflammatory drugs appear to be diverse. Phenylbutazone and sulfmpyrzone inhibited several effects of FMLP on PMNs increased adhesiveness, stimulation of the hexosemonophosphate shunt, lysosomal enzyme release, and formation of O These effects were explained by the ability of both phenylbutazone and sulfinpyrazone to inhibit binding of labelled FMLP to PMNs. Both were selective in that neither inhibited responses of PMNs to Csa and neither inhibited the stimulation of the hexose monophosphate shunt by latex or by opsonized Candida. The responses of PMNs to FMLP, including the release of O have also been inhibited by 5,8,11,14 eicosatetraynoic acid, an inhibitor of the metabolism of arachidonic acid h by indomethacin and by... 

Hydroquinone binding to calf thymus DNA and cysteine is enhanced by oxidation (prostaglandin H synthetase or cumene hydroperoxide) and inhibited by indomethacin... 

Indomethacin is absorbed after oral administration reaching peak plasma concentrations after 2 h. About 99% binds to plasma proteins and it has a variable terminal half-life from 2.6 to 11.2 h in adults and up to 30 h in neonates. The metabolites generated in the liver are desmethyl-indomethacin, desbenzoyl-indomethacin,... 

Warfarin, Indomethacin, and Phenylbutazone—these compounds share a single high-affinity site that differs from those described above. They share a secondary site that is identical to or overlaps with that for tryptophan as described above. Salicylate—two primary binding sites. One is identical to or overlaps the tryptophan binding site and the other is identical to or overlaps the high-affinity site for warfarin, indomethacin, and phenylbutazone as described above. 

These studies provide evidence for at least four binding sites in HSA one for tryptophan, that also interacts strongly with many other compounds one that appears to be very specific for bilirubin one high-affinity site for palmitate and one high-affinity site for warfarin, indomethacin, phenylbutazone, and a number of other drugs (i.e. see Ref. 36). Each of these sites appears to be separate and distinct from each of the others. 

There are two major groups of synthetic compounds which have cannabin-oid activity, but which differ chemically from the tricyclic THC-like canna-binoids the bicyclic cannabinoids, exemplified by compound CP55940 (23), and the (aminoalkyl)indoles exemplified by pravadoline (24a). A detailed SAR analysis of these groups of compounds is beyond the scope of this review. The bicyclic cannabinoids and derivatives have been reviewed previously [105] recent publications deal mainly with related tricyclic non-classical cannabinoids [106] and with the (aminoalkyl)indoles [92, 107]. It is of interest to note that while the bicyclic cannabinoids were originally prepared as simplified cannabinoids, the cannabinoid-type activity of the (ami-noalkyl)indoles was discovered by serendipity. These compounds were synthesized in a project aimed at the discovery of novel nonsteroidal anti-inflammatory agents presumably based on the indomethacin structure. However, while they did not possess anti-inflammatory properties, they were found to be antinociceptive, and to inhibit the electrically evoked contractions in a mouse vas deferens muscle preparation. This led to binding experi-... 

Figure 3 Structural basis of COX inhibition by a-substituted indomethacin ethanolamides. Structures and inhibitory activities of indomethacin and the a-ethyl indomethacin ethanolamides are shown. The crystal structures of indomethacin bound to COX-2 and 8 and 9 bound to COX-1 reveal differences in the binding of the R- and 5-enantiomers to COX-1.

Less extensive binding of drugs to plasma proteins is generally without clinical importance but there is a significant risk of elevation of plasma bilirubin (in the neonate) following its displacement from protein binding sites by vitamin K, x-ray contrast media or indomethacin. 

Bilirubin is displaced from its binding protein by sulphonamides, vitamin K, X-ray contrast media or indomethacin in the neonate this may cause a significant risk of kernicterus, for its capacity to metabolise bilirubin is immature. 

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