Effect of fenclofenac on prostaglandin production in carageenin air bleb exudates in rats

Abstract

Employing a modified carrageenin air bleb technique in rats, the effect was studied of fenclofenac and standard drugs (acetylsalicylic acid, indomethacin and phenylbutazone) on prostaglandin production in inflammatory exudate. In common with the standard drugs, fenclofenac reduced exudate prostaglandin levels, being approximately equipotent with phenylbutazone in this respect. Also, an attempt was made to relate the effect of fenclofenac and standard drugs on prostaglandins to their acute anti-inflammatory activity as determined in a modified carrageenin paw oedema test in rats. Whilst acetylsalicylic acid and phenybutazone significantly inhibited oedema at doses producing 80% inhibition of prostaglandin production in air bleb exudate, fenclofenac and indomethacin did not. The overall results were considered to support the view expressed by other workers that the acute anti-inflammatory activity of acidic anti-inflammatory agents does not result solely, if at all, from inhibition of prostaglandin synthesis.

Novel Anti-Inflammatory Agents

“…As mentioned before, fenclofenac [a close analogue of fcnoprofen (Lilly)], first thought to be of the classical type (49) has now been found to modulate the immune system (43). Again in animal studies, this product was found to have minimal activity in the acute but strong activity in the chronic assays.…”

Nonsteroidal acidic anti-inflammatory agents: Do they constitute a single drug class?

“…These apparent qualitative similarities have no doubt contributed to the wide acceptance of the unifying hypothesis that the biological activities of these agents result from their common ability to inhibit prostaglandin biosynthesis [1][2][3]. Whilst this hypothesis has been seriously questioned from several quarters [4][5][6], it is still generally believed that their activities result from the same combination of mechanisms, if not solely from their effects on prostaglandins. Thus, by extrapolation, it might be expected that, in terms of clinical efficacy (as opposed to potency), none of these NSAAIAs is likely to have any significant advantage over any other in the same class, all having merely a palliative action in rheumatic diseases.…”

Adrenocortical stimulation and the anti-inflammatory actions of salicylates

“…Evidence accumulated over the last decade has led to a hypothesis that their mode of action resides in the ability of the drugs to inhibit the production of biologically active lipids from arachidonic acid by inhibiting prostaglandin cyclooxygenase (Ferreira & Vane 1979;Vane 1978). Whilst this effect is not disputed, there is now available a substantial literature which would argue that other antiinflammatory actions of these drugs, particularly those directed against leucocyte accumulation in inflammatory exudates, are unrelated to their effects on prostaglandin cyclo-oxygenase (Walker et al 1976;Glenn et a1 1977;Atkinson & Leach 1978;Smith 1978).…”