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Figure 1.

Structures of ibuprofen, flurbiprofen and the metabolites investigated in the present study.

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Figure 2.

Inhibition of the activities of ovine COX-1 (towards arachidonic acid) and human recombinant COX-2 (towards either arachidonic acid or 2-AG) by ibuprofen and its 2′- and 3′-hydroxy metabolites.

The substrates used (10 µM) are shown in the figure, as are the concentrations (in µM) of the test compounds. “F30” refers to 30 µM flurbiprofen, used as a positive control. Values are means ± s.e.m. (unless enclosed by the symbols), n = 3, of the change in oxygen utilisation following addition of enzyme to the oxygen electrode chamber.

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Figure 2 Expand

Figure 3.

Inhibition of the activities of ovine COX-1 (towards arachidonic acid) and human recombinant COX-2 (towards either arachidonic acid or 2-AG) by flurbiprofen and its 4′-hydroxy metabolite.

The substrates used (10 µM) are shown in the figure, as are the concentrations (in µM) of the test compounds. Values are means ± s.e.m. (unless enclosed by the symbols), n = 3, of the change in oxygen utilisation following addition of enzyme to the oxygen electrode chamber.

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Figure 3 Expand

Table 1.

Comparison of the effects of the NSAIDs and their metabolites upon the initial activity of COX-1.

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Table 1 Expand

Table 2.

Comparison of the effects of the NSAIDs and their metabolites upon the initial activity of COX-2.

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Table 2 Expand

Figure 4.

Inhibition of FAAH activity in rat brain homogenates by ibuprofen and its 1′-OH, 2′-OH, 3′-OH and carboxy metabolites.

The AEA assay concentration was 0.5 µM. Values are means ± s.e.m. (unless enclosed by the symbols), n = 3.

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Figure 4 Expand

Figure 5.

Inhibition of FAAH activity in rat brain homogenates by A, flurbiprofen and its 4′-hydroxy metabolite.

The AEA assay concentration was 0.5 µM. Values are means ± s.e.m. (unless enclosed by the symbols), n = 3.

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Figure 5 Expand

Table 3.

pI50 and IC50 values for ibuprofen, flurbiprofen and their metabolites towards the inhibition of 0.5 µM [3H]AEA hydrolysis by rat brain FAAH.

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Table 3 Expand