Inhibition of prostaglandin biosynthesis by non-narcotic analgesic drugs.

The existence of a relationship between inhibition of prostaglandin biosynthesis and analgesic or anti-inflammatory activity was investigated in the case of the non-narcotic analgesics glafenine, floctafenine and clometacine, in comparison to indomethacin and acetylsalicylic acid. These compounds inhibit prostaglandin biosynthesis from arachidonic acid in a guinea-pig lung homogenate as strongly as indomethacin. On its biosynthesis in rat epididymal tissue stimulated by noradrenaline, glafenine equals indomethacin inhibitory potency, whereas floctafenine and clometacine are less active. Acetylsalicylic acid is the least active in both preparations. In vivo, prostaglandin biosynthesis induced in rat peritoneal fluid by injection of acetic acid is inhibited by the 5 drugs, ranked as follows: floctafenine greater than indomethacin greater than glafenine greater than clometacine greater than acetylsalicylic acid. The pharmacological profile of glafenine, floctafenine and clometacine is characterized by a relatively strong effect on acetic acid writhing and a relatively weak effect on carrageenin oedema, U.V. erythema and adjuvant arthritis. The inhibition of prostaglandin biosynthesis seems better correlated with their analgesic activity than with their anti-inflammatory effects. The results show that prostaglandins could play an important role in the genesis of tissulary pain in animals.

Floctafenine, a new non-narcotic analgesic.

Floctafenine has been studied in comparison with acetyl-salicylic acid, indomethacin and d-propoxyphene in a series of tests for analgesic and anti-inflammatory activity. It is very active in the acetic acid-induced writhing test and on the inflamed paw in the Randall and Selitto test. Furthermore, like acetylsalicylic acid and indomethacin, but unlike d-propoxyphene, it has no effect on the non-inflamed paw, and similarly it is inactive in the tail flick and in the hot plate test. Floctafenine is also very effective in some acute inflammations such as naphtoylheparamine-induced oedema or in UV erythema, but it is distinctly less active in carrageenin-induced oedema or in adjuvant arthritis. In rat gastric and intestinal mucosa its tolerance is excellent. It has no action on the central and autonomous nervous systems. The pharmacological profile of this compound thus places it amongst the non-narcotic analgesics. It has an exceptionally high therapeutic index, much higher than that of acetylsalicylic acid and indomethacin.