Anti-inflammatory and related properties of 2-(2,4-dichlorophenoxy)phenylacetic acid (fenclofenac)

Abstract

Fenclofenac was shown to possess anti-inflammatory, antinociceptive and antipyretic properties as measured by tests in rats that detect clinically active compounds. In a chronic test for assessing anti-inflammatory activity (established adjuvant arthritis), it was approximately equipotent to alclofenac, fenoprofen calcium and phenylbutazone, more potent than acetylsalicylic acid and ibuprofen, but was less potent than diclofenac sodium, indomethacin, ketoprofen and naproxen. In contrast, the potency of fenclofenac in acute tests for anti-inflammatory, antinociceptive and anti-pyretic activity was generally lower, the drug being approximately equipotent to acetylsalicylic acid in such tests. The anti-inflammatory activity of fenclofenac was not mediated via the pituitary-adrenal axis or a counter-irritant action. Fenclofenac was shown to have remarkably low gastric ulcerogenic potential, both acutely and chronically.

Biodistribution of mild analgesics.

“…An analysis of the chemical nature of the labelled molecules in the different compartments of interest is in preparation. We have confirmed our previous observations concerning the specific biodistribution of acidic, antiinflammatory analgesics using near adult rats (120 g) at high, clearly anti-inflammatory doses (see also the data of Atkinson & Leach, 1976). Even at these doses considerably higher concentrations (for example, three times with indomethacin) of labelled drug were found in the inflamed paw compared with the control.…”

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

“…Firstly, fenclofenac failed to exert a significant inhibitory effect on carrageenin paw oedema at doses which markedly inhibit prostaglandin production induced by the same irritant. Secondly, fenclofenac and phenylbutazone were apparently equipotent as inhibitors of carrageenininduced prostaglandin release yet previous studies have shown that phenylbutazone was significantly more potent than fenclofenac in the carrageenin oedema test [9]. Thus it would appear that the anti-oedema activity of fenclofenac is mediated by either an additional or alternative mechanism which becomes operative at doses in excess of those required to suppress prostaglandin release.…”

“…It was, therefore, of interest to determine whether fenclofenac, a recently developed nonsteroidal anti-inflammatory agent [8,9], inhibited prostaglandin production and to ascertain whether such activity could account for its antiinflammatory properties. For this purpose, studies have been undertaken to see if fenclofenac lowers prostaglandin levels in rat inflammatory exudate and to compare such activity with that of standard drugs.…”

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

“…Fenclofenac ( Fig. 1), a recently developed NSAAIA [10,11], appears to be qualitatively different from ASA in its effects on the gastric mucosa of guinea pigs when administered intragastrically [12]. Whereas at pH 7.4 ASA produced minimal mucosal cell exfoliation and shallow gastric erosions, fenclofenac induced marked cellular exfoliation but no erosions.…”

“…However, many NSAAIAs, including ASA, indomethacin, phenylbutazone and fenclofenac, reduce elevated plasma fibrinogen levels in rats with adjuvant arthritis [11,21]. This raises the possibility that the apparently selective effect of alclofenac, fenclofenac and ICI 55,897 on ESR and related parameters in rheumatoid patients is merely a reflection of a higher level of anti-inflammatory activity and not of some novel antirheumatic action.…”