Inhibitory effect of N,O-acil-threo-DL-phenylserine derivatives on rat adjuvant arthritis.

ABSTRACT

Rat adjuvant arthritis (AA), a model of chronic inflammation and an experimental model of rheumatoid arthritis (RA) has been used to evaluate the possible anti-inflammatory action of seventeen N,O-acil-threo-DL-phenylserines 1-17. For this purpose experiments on 200 male Wistar rats were performed. The obtained results showed that oral administration of all compounds, except 15, inhibited the development of AA as compared with the control group. Although the level of arthritic suppression of some preparations was equivalent to aspirin or exceeded it (compounds 2-4, 6, 10, 13), only the preparation 10 in a dose of 100 mg/kg significantly change the paw swelling (P < 0.02) which decreased by 27.9-31.7% at the end of experiment. Pronounced inhibition (P < 0.05-0.01) of joint swelling and the indices of pathological process activity were revealed in earlier stages of AA under the treatment with compounds such as 6 and 11. The antiinflammatory effect of some compounds (9, 11, 13) was observed in the middle of the experiment, although only compound 9 showed significant suppression by 35.9-37.9% at this stage (P < 0.01-0.001) which also markedly decreased ESR (P < 0.05). The latter index was significantly reduced by the action of preparations 2-4, 6-8. Most of the compounds investigated improved blood indices and prevented the development of polyarthritis.