Anti-inflammatory properties of N-phenylanthranilic acid derivatives in relation to uncoupling of oxidative phosphorylation.

It has been known that a variety of non-steroidal anti-inflammatory drugs uncouple oxidative phosphorylation in mitochondria (1-5). Adams and Cobb (2) have studied whether or not the inhibition of inflammation by non-steroidal drugs was related to their in vitro capacity to uncouple oxidative phosphorylation. Whitehouse (6) has made an extensive survey on this problem. We have reported that a variety of non-steroidal anti-inflammatory drugs inhibit the degranulation of isolated mast cells of the rat, which is blocked by uncouplers of oxidative phosphorylation as well as by inhibitors of the respiratory chain (7). It was then found that anti-inflammatory activity of these drugs bore quantitative relation to their in vitro capacity to inhibit the degranulation. In addition, anti-inflammatory effect of 2,4-dinitro phenol, dicoumarol and warfarin was also demonstrated. These results appear to favor the hypothesis proposed by Whitehouse (6) that the uncoupling activity of non-steroidal anti-inflammatory drugs may be causally related to their inhibitory effect on inflammation. Flufenamic acid [N-(3-trifluoromethyl phenyl) anthranilic acid; Fig. 1, R1=H, R 2 = CF3] and mefenamic acid [N-(2,3-di methylphenyl) anthranilic acid; Fig. 1, R1 = CH, R 2 = CH 3] have proven to have