SYNTHESIS AND EVALUATION OF THE ANTIINFLAMMATORY EFFECTS OF NIFLUMIC ACID LIPOPHILIC PRODRUGS IN BRAIN EDEMA

Five new lipophilic prodrugs of the non-steroidal anti-inflammatory dr ug, niflumic acid (Nifluril(R), CAS 4394-00-7). were synthetized and e valuated on the experimental brain edema (injection of phospholipase A (2)). The effect of these drugs in comparison with dexamethasone which elicits a marked effect on clinical and experimental brain edema was evaluated. Niflumic acid was vectorised by cholesterol, hexadecanol an d by three 1,3-diacylglycerols. The anti-inflammatory activity of thes e compounds on experimental brain edema was evaluated by determination of the prostaglandin E(2) (PGE(2)) brain tissue concentration. Niflum ic acid reduced the prostaglandin E(2) production more significantly t han dexamethasone. Niflumic acid prodrug forms [2-[3-(trifluoromethyl) anilino]nicotinoyl]glycerol and luoromethyl)anilino]nicotinoyloxybutan oyl]glycerol also showed a marked anti-inflammatory activity at low co ncentrations.