An unusual profile of activity of a new basic anti-inflammatory drug, timegadine

Abstract

Timegadine (SR 1368, N-cyclohexyl-N"-4-(2-methylguinolyl)-N'-2-thiazolylguanidine) dose-dependently inhibited carrageenan-, nystatin-, and concanavalin A-induced edema. Detailed studies in adjuvant arthritic rats showed: (a) long dosing regimen with timegadine inhibited primary and secondary lesions, leukocytosis and hyperfibrinogemia, (b) timegadine was significantly active in reducing the severity of the already established disease, (c) a short course of dosing with timegadine at the time of adjuvant injection permanently prevented the development of secondary lesions. The tuberculin hypersensitivity reaction was enhanced by timegadine in both adjuvant arthritic and normal rats. Experimental allergic encephalomyelitis in rats and guinea pigs was not affected. It is concluded that timegadine has a profile or activity which differs from that of known anti-inflammatory drugs.

Drug actions on delayed-type hypersensitivity in rats with developing and established adjuvant arthritis

“…The non-steroidal anti-inflammatory agents indomethacin and tiaprofenic acid had a different profile of activity with no effect on DTH at either timepoint, and inhibition of AA as expected for agents of this type [21]. Indomethacin has similarly been reported to have no effect on DTH or depressed lymphocyte mitogenesis in this model [7,17,18]. The clinically active anti-arthritis agents chloroquine, levamisole and D-penicillamine failed to modify DTH or AA.…”

Effect of α-(3,5-Di-Tert-Butyl-4-Hydroxybenzylidene)-γ-Butyrolactone (KME-4), a New Anti-Inflammatory Drug, on the Established Adjuvant Arthritis in Rats

“…BW755C (12) and timegadine (16, 17) have been reported to be dual inhibitors of arachidonic acid metabolism. In fact, BW755C shows a different effect from indomethacin in reducing leukocyte migration in the rat carrageenin sponge model (12, 18), and the anti-inflammatory effect of timegadine on adjuvant arthritis in rats differs from those of known some NSAIDs (19). In addition, benoxaprofen which is also a lipoxygenase inhibitor with a weak inhibition of prosta glandin biosynthesis (20)(21)(22) has been shown to produce a greater effect than many NSAIDs at nontoxic doses in suppressing the bone damage of adjuvant arthritis in rats, and it has been suggested that its effect is through a suppression of leukocyte migration into the inflammatory site by inhibiting lipoxygenase (11).…”

Novel Anti-Inflammatory Agents

“…A confirmation of this is the (17). In in uivo experiments with rat inflamed exudate it produced, at 4 mg/kg PO, an increase (69%) in total PG-like substances, while indomethacin, at 0.2 mg/kg, under the same conditions, produced a decrease (-72%) of the same substances.…”